With the use of 2 independent techniques, circulating monomeric and oligomeric IgM were detected ... more With the use of 2 independent techniques, circulating monomeric and oligomeric IgM were detected in the majority of 29 patients with chronic lymphocytic leukemia (CLL). In contrast it was detected only in trace quantities in a minority of healthy subjects. In the CLL group no significant correlation was observed between monomeric IgM and the total serum IgM level or the absolute lymphocyte count. Mitogen stimulated peripheral blood mononuclear cells from CLL patients were observed to secrete monomeric and oligomeric IgM in-vitro. Experiments manipulating the microenvironment of an IgM secreting cell line revealed that the addition of low concentrations of the reducing reagent 2-mercaptoethanol to the culture medium would enhance the proportions of monomeric IgM in the culture supernatant and the cellular cytoplasmic lysate. However the same concentrations would not directly reduce the secreted IgM. We conclude that the secretion of incompletely assembled IgM is commonly found in CLL and suggests an intrinsic defect(s) in the mechanisms involved in the polymerization of the monomeric units into the pentameric molecule.
A Royal College of Pathologists of Australasia (RCPA) sponsored Quality Assurance Program (QAP) i... more A Royal College of Pathologists of Australasia (RCPA) sponsored Quality Assurance Program (QAP) in Clinical Immunology, involving 128 laboratories over a 1 yr period, revealed the following: successful participation in the program by 16 overseas laboratories (distant from Australia); only 30% of laboratories succeeded in returning their results by the scheduled date on every occasion; quantitation of urinary total protein and Bence Jones protein was poor and varied over a log scale; immunofixation was more successful in characterizing urinary paraprotein than immunoelectrophoresis; densitometry of protein electrophoresis appeared the method of choice in quantitating serum paraproteins accurately; nephelometric techniques gave better concordance between laboratories than turbidometric, radial immunodiffusion or agglutination techniques; poor concordance between laboratories in detecting weakly positive antinuclear antibodies (ANA); some laboratories had difficulties in identifying ANA patterns (only 60% of laboratories correctly identified the anticentromere pattern); few laboratories could correctly identify antibodies to extractable nuclear antigens (ENA); flow cytometry gave a smaller dispersion of lymphocyte subpopulation percentages than microscopy. A method was established to rank laboratory performance of selected tests over the 1 yr period. Such a comparative ranking scheme may alert laboratories in identifying specific or generalized deficiencies in performance.
The long-terms complications of immunosuppressive and anti-inflammatory treatment in idiopathic i... more The long-terms complications of immunosuppressive and anti-inflammatory treatment in idiopathic inflammatory myositis (IIM) are unknown. We sought to determine the complications of these treatments in a large cohort of patients with biopsy-proven IIM. A South Australian database for patients with biopsy-proven IIM was established. Clinical details of patients including treatment received were recorded. Forty-three patients with dermatomyositis (DM), 184 with polymyositis (PM) and 117 with inclusion body myositis (IBM) were registered on the database. The prevalence of hypertension and diabetes in this population was 62% and 29%, respectively, considerably higher than the background prevalence of 9.4% and 4%, making detection of treatment-related adverse effects difficult. Hypertension and ischemic heart disease were more likely to be present prior to the diagnosis of IIM rather than following it. Hypertension and diabetes occurred more frequently following the diagnosis of myositis, in patients with DM compared with PM or IBM. We report a novel association of IIM with hypertension, diabetes and ischemic heart disease, indicating that a comprehensive assessment of vascular risk factors is essential in IIM.
Background Crusted scabies is a rare and severely debilitating disease characterized by infestati... more Background Crusted scabies is a rare and severely debilitating disease characterized by infestation of the skin with up to millions of Sarcoptes scabiei mites, high total IgG levels, extremely high total IgE levels, and the development of hyperkeratotic skin crusts that may ...
Monoclonal antibodies specific for lymphocyte subsets were used to examine circulating lymphocyte... more Monoclonal antibodies specific for lymphocyte subsets were used to examine circulating lymphocytes obtained at frequent intervals from healthy subjects. A diurnal rhythm was found in the total numbers of lymphocytes, T cells, inducer/helper cells, suppressor/cytotoxic cells, Ia positive cells, and B cells. The lowest levels of all subsets were seen at 0900 hours and the highest levels at 2100. In some subjects the ratio of helper to suppressor cells varied considerably during the sample period, though the ratio was relatively constant for the group as a whole.
The majority of paired sera and synovial fluids from 21 patients with rheumatoid arthritis produc... more The majority of paired sera and synovial fluids from 21 patients with rheumatoid arthritis produced a rapid chemiluminescent response when incubated with human neutrophils. Synovial fluid gave considerably higher responses than the paired serum specimen. In contrast little or no response was found with paired sera and joint fluid taken from patients with gout, psoriasis, and osteoarthritis and with sera from healthy donors. A similar chemiluminescent response was observed when neutrophils were preincubated with large aggregates of heated human gammaglobulin (HAGG), which were used as a model of immune complexes. Smaller nonreactive aggregates of gammaglobulin became reactive after preincubation with a purified monoclonal rheumatoid factor (mRF) which had a high avidity for aggregated IgG. The addition of this monoclonal rheumatoid factor also caused enhancement of chemiluminescence by rheumatoid sera. Further evidence suggesting that the active material found in these rheumatoid specimens contained complexed immunoglobulin was obtained by indirect immunofluorescence. Neutrophils developed intracellular immunoglobulin inclusions after preincubation in reactive rheumatoid sera but not with nonreactive or normal sera. However, activation of neutrophil chemiluminescence by rheumatoid specimens did not correlate significantly with levels of rheumatoid factor or immune complexes suggesting that the activating complexes were of a particular type. In conclusion we have shown the direct activation of neutrophil chemiluminescence by rheumatoid sera synovial fluid and suggest that the activation is caused by large IgG-containing immune complexes. It is possible that this activation may have important implications in the immunopathogenesis of the rheumatoid inflammatory process.
In a cross-sectional study of over 3000 consecutive serum specimens the levels of rheumatoid fact... more In a cross-sectional study of over 3000 consecutive serum specimens the levels of rheumatoid factor (RF) measured by rate nephelometry (Beckman ICS II) were compared with values obtained by the more traditional methods of sheep cell agglutination (Rose-Waaler) and latex agglutination. Similar values for sensitivity and specificity were found for all three methods for rheumatoid arthritis, with nephelometry giving slightly higher levels of sensitivity for other rheumatic disorders. A significant correlation (r = 0.46, p less than 0.01) was found between the nephelometric and Rose-Waaler method for 147 consecutive seropositive specimens. Of interest, however, several disparate results were observed, and explanations for these were sought. Longitudinal studies of RF were performed in 49 seropositive patients over a two-year period. The nephelometric method was considered superior compared with the other techniques because of its ability to detect changes in absolute levels at earlier stages and its low interassay coefficient of variance (11%). We conclude that the nephelometric technique appears suitable for routine diagnostic use, offers several advantages compared with more traditional methods, and is no more expensive per test specimen than the Rose-Waaler technique.
To evaluate the role of low molecular weight (LMW) IgM and CD5 B cells in rheumatoid arthritis (R... more To evaluate the role of low molecular weight (LMW) IgM and CD5 B cells in rheumatoid arthritis (RA) and to explore the possibility that LMW IgM is derived selectively from this subset of B cells. LMW IgM in sera and culture supernatants was detected by a sensitive immunoblot technique with an enhanced chemiluminescence detection system. CD5 B cells were determined by FACScan cytometry. In vitro studies were established in culture plates containing pokeweed mitogen with or without 2-mercaptoethanol (2-ME). Supernatants were obtained from CD5 positive hybridomas and CD5 negative hybridomas. Other immunological indices were measured by laser nephelometry. Circulating LMW IgM was detected in all rheumatoid patients with significantly higher levels being observed in sero-positive patients. LMW IgM correlated significantly with total IgM and RF. Peripheral blood mononuclear cells (PBMC) from the majority of the patients with RA secreted LMW IgM in vitro as did mononuclear cells from a synovial fluid sample. The addition of low concentrations of 2-ME to the culture medium enhanced the proportions of secreted monomeric IgM. In contrast, PBMC from healthy subjects secreted only trace quantities of LMW IgM. In RA no significant correlations were observed between CD5 B cells and LMW IgM and RF. LMW IgM could be detected in the supernatants from both CD5+ and CD5- B cell lines. Finally, CD5 B cells were not significantly elevated in RA and levels remained constant over time. LMW IgM exists in high concentrations in RA sera and synovial fluid. Serum level correlates with RF and IgM. In vitro studies have suggested that the occurrence of LMW IgM may be due to an intrinsic defect(s) in the assembly of the IgM pentameric molecule. LMW IgM is unlikely to be derived solely from CD5 B cells.
To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well a... more To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well as their clinical associations, in a well-characterized Australian patient cohort. Serum from 505 Australian SSc patients were analyzed with a commercial line immunoassay (EuroLine; Euroimmun) for autoantibodies to centromere proteins CENP-A and CENP-B, RNA polymerase III (RNAP III; epitopes 11 and 155), the 90-kd nucleolar protein NOR-90, fibrillarin, Th/To, PM/Scl-75, PM/Scl-100, Ku, topoisomerase I (topo I), tripartite motif-containing protein 21/Ro 52, and platelet-derived growth factor receptor. Patient subgroups were identified by hierarchical clustering of the first 2 dimensions of a principal components analysis of quantitative autoantibody scores. Results were compared with detailed clinical data. A total of 449 of the 505 patients were positive for at least 1 autoantibody by immunoblotting. Heatmap visualization of autoantibody scores, along with principal components analysis clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP III, and topo I. Five patient clusters were identified: CENP, RNAP III strong, RNAP III weak, topo I, and other. Clinical features associated with CENP, RNAP III, and topo I were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP III into 2 clusters. Patients in the RNAP III strong cluster had an increased risk of gastric antral vascular ectasia, but a lower risk of esophageal dysmotility. Patients in the other cluster were more likely to be male and to have a history of smoking and a history of malignancy, but were less likely to have telangiectasia, Raynaud's phenomenon, and joint contractures. Five major autoantibody clusters with specific clinical and serologic associations were identified in Australian SSc patients. Subclassification and disease stratification using autoantibodies may have clinical utility, particularly in early disease.
Australian and New Zealand journal of medicine, 1999
The mitotic spindle apparatus (MSA) is a unique structure of microtubules and associated proteins... more The mitotic spindle apparatus (MSA) is a unique structure of microtubules and associated proteins involved in the segregation and reorganisation of chromosomes during cell division. Autoantibodies to the MSA (anti-MSA) are reported to occur rarely, but are easily identified during the immunofluorescent detection of anti-nuclear antibodies (ANA), and are generally reported as part of that investigation. As the clinical significance of these antibodies is unknown, our aim was to identify the clinical features of subjects identified with anti-MSA, and in a subset investigate the co-association with organ specific anti-thyroid antibodies. All ANA results from the three major immunology laboratories serving South Australia between January 1993 and June 1998 were retrospectively reviewed to identify anti-MSA subjects. Clinical details were extracted from hospital or general practice records using a standard proforma. Thyroid autoantibodies were measured using standard technique. A control...
Australian and New Zealand journal of medicine, 1996
The clinical associations of anti-lamin autoantibodies were first described in 1973. Since then a... more The clinical associations of anti-lamin autoantibodies were first described in 1973. Since then a number of individual case reports and two small series have been published. These have suggested an association with connective tissue disorders and autoimmune liver disease. To identify the clinical and laboratory associations of anti-lamin autoantibodies in an Australian population. Retrospective review of routine antinuclear antibody testing between 1990-1994 for characteristics linear staining of nuclear envelope on indirect immunofluorescence on HEp-2 cells with clinical status defined by retrospective review of case records. Twenty-eight patients were identified and the clinical status of 27 patients defined. Eleven patients had associated IgG anti-cardiolipin antibodies; anti-phospholipid syndrome was present in nine. Seven further patients had liver disease; five had autoimmune liver disease, with associated autoantibodies. The remaining nine patients had a diverse group of dise...
Previous studies have demonstrated an increased risk of breast cancer among patients with systemi... more Previous studies have demonstrated an increased risk of breast cancer among patients with systemic sclerosis (scleroderma). To describe the clinical characteristics of 21 patients with both systemic sclerosis and breast cancer, and compare their risk factors to female scleroderma patients without breast cancer, in a population-based cohort study of South Australia. Subjects with scleroderma and breast cancer were identified from the South Australian Scleroderma Register with cross-linking to the South Australian Cancer Registry, last updated to the end of December 2005. Clinical information was obtained from standardised self-administered questionnaires and case note reviews. Odds ratios for the risk factors for breast cancer in scleroderma were determined, and clinical variables were analysed using chi square, Fisher's exact, Mann-Whitney and t tests. At the end of December 2005 there were a total of 389 female patients with scleroderma. Of these, 21 (5.4%) had been diagnosed with breast cancer. The mean age of onset of scleroderma was 43.5 years, and the mean age of breast cancer was 60.5 years in those with scleroderma and breast cancer. The majority (71.4%) had limited scleroderma, with anti-centromere antibody being the most prevalent serological abnormality. In 16 (76%) patients the diagnosis of breast cancer occurred on an average of 22.3 years after the onset of their first scleroderma symptom. When compared to 48 controls, scleroderma patients with breast cancer were found to have a higher incidence of a positive family history of breast cancer (Fisher's exact test, p = 0.04) and a lower incidence of hormone-replacement therapy use (Fisher's exact test, p = 0.0026). This population-based cohort study provides evidence that the majority of patients with scleroderma and breast cancer have limited scleroderma and anti-centromere antibody. Given the increased incidence of solid tumours in systemic sclerosis, we suggest regular screening of female patients for breast cancer, especially in those with a family history.
With the use of 2 independent techniques, circulating monomeric and oligomeric IgM were detected ... more With the use of 2 independent techniques, circulating monomeric and oligomeric IgM were detected in the majority of 29 patients with chronic lymphocytic leukemia (CLL). In contrast it was detected only in trace quantities in a minority of healthy subjects. In the CLL group no significant correlation was observed between monomeric IgM and the total serum IgM level or the absolute lymphocyte count. Mitogen stimulated peripheral blood mononuclear cells from CLL patients were observed to secrete monomeric and oligomeric IgM in-vitro. Experiments manipulating the microenvironment of an IgM secreting cell line revealed that the addition of low concentrations of the reducing reagent 2-mercaptoethanol to the culture medium would enhance the proportions of monomeric IgM in the culture supernatant and the cellular cytoplasmic lysate. However the same concentrations would not directly reduce the secreted IgM. We conclude that the secretion of incompletely assembled IgM is commonly found in CLL and suggests an intrinsic defect(s) in the mechanisms involved in the polymerization of the monomeric units into the pentameric molecule.
A Royal College of Pathologists of Australasia (RCPA) sponsored Quality Assurance Program (QAP) i... more A Royal College of Pathologists of Australasia (RCPA) sponsored Quality Assurance Program (QAP) in Clinical Immunology, involving 128 laboratories over a 1 yr period, revealed the following: successful participation in the program by 16 overseas laboratories (distant from Australia); only 30% of laboratories succeeded in returning their results by the scheduled date on every occasion; quantitation of urinary total protein and Bence Jones protein was poor and varied over a log scale; immunofixation was more successful in characterizing urinary paraprotein than immunoelectrophoresis; densitometry of protein electrophoresis appeared the method of choice in quantitating serum paraproteins accurately; nephelometric techniques gave better concordance between laboratories than turbidometric, radial immunodiffusion or agglutination techniques; poor concordance between laboratories in detecting weakly positive antinuclear antibodies (ANA); some laboratories had difficulties in identifying ANA patterns (only 60% of laboratories correctly identified the anticentromere pattern); few laboratories could correctly identify antibodies to extractable nuclear antigens (ENA); flow cytometry gave a smaller dispersion of lymphocyte subpopulation percentages than microscopy. A method was established to rank laboratory performance of selected tests over the 1 yr period. Such a comparative ranking scheme may alert laboratories in identifying specific or generalized deficiencies in performance.
The long-terms complications of immunosuppressive and anti-inflammatory treatment in idiopathic i... more The long-terms complications of immunosuppressive and anti-inflammatory treatment in idiopathic inflammatory myositis (IIM) are unknown. We sought to determine the complications of these treatments in a large cohort of patients with biopsy-proven IIM. A South Australian database for patients with biopsy-proven IIM was established. Clinical details of patients including treatment received were recorded. Forty-three patients with dermatomyositis (DM), 184 with polymyositis (PM) and 117 with inclusion body myositis (IBM) were registered on the database. The prevalence of hypertension and diabetes in this population was 62% and 29%, respectively, considerably higher than the background prevalence of 9.4% and 4%, making detection of treatment-related adverse effects difficult. Hypertension and ischemic heart disease were more likely to be present prior to the diagnosis of IIM rather than following it. Hypertension and diabetes occurred more frequently following the diagnosis of myositis, in patients with DM compared with PM or IBM. We report a novel association of IIM with hypertension, diabetes and ischemic heart disease, indicating that a comprehensive assessment of vascular risk factors is essential in IIM.
Background Crusted scabies is a rare and severely debilitating disease characterized by infestati... more Background Crusted scabies is a rare and severely debilitating disease characterized by infestation of the skin with up to millions of Sarcoptes scabiei mites, high total IgG levels, extremely high total IgE levels, and the development of hyperkeratotic skin crusts that may ...
Monoclonal antibodies specific for lymphocyte subsets were used to examine circulating lymphocyte... more Monoclonal antibodies specific for lymphocyte subsets were used to examine circulating lymphocytes obtained at frequent intervals from healthy subjects. A diurnal rhythm was found in the total numbers of lymphocytes, T cells, inducer/helper cells, suppressor/cytotoxic cells, Ia positive cells, and B cells. The lowest levels of all subsets were seen at 0900 hours and the highest levels at 2100. In some subjects the ratio of helper to suppressor cells varied considerably during the sample period, though the ratio was relatively constant for the group as a whole.
The majority of paired sera and synovial fluids from 21 patients with rheumatoid arthritis produc... more The majority of paired sera and synovial fluids from 21 patients with rheumatoid arthritis produced a rapid chemiluminescent response when incubated with human neutrophils. Synovial fluid gave considerably higher responses than the paired serum specimen. In contrast little or no response was found with paired sera and joint fluid taken from patients with gout, psoriasis, and osteoarthritis and with sera from healthy donors. A similar chemiluminescent response was observed when neutrophils were preincubated with large aggregates of heated human gammaglobulin (HAGG), which were used as a model of immune complexes. Smaller nonreactive aggregates of gammaglobulin became reactive after preincubation with a purified monoclonal rheumatoid factor (mRF) which had a high avidity for aggregated IgG. The addition of this monoclonal rheumatoid factor also caused enhancement of chemiluminescence by rheumatoid sera. Further evidence suggesting that the active material found in these rheumatoid specimens contained complexed immunoglobulin was obtained by indirect immunofluorescence. Neutrophils developed intracellular immunoglobulin inclusions after preincubation in reactive rheumatoid sera but not with nonreactive or normal sera. However, activation of neutrophil chemiluminescence by rheumatoid specimens did not correlate significantly with levels of rheumatoid factor or immune complexes suggesting that the activating complexes were of a particular type. In conclusion we have shown the direct activation of neutrophil chemiluminescence by rheumatoid sera synovial fluid and suggest that the activation is caused by large IgG-containing immune complexes. It is possible that this activation may have important implications in the immunopathogenesis of the rheumatoid inflammatory process.
In a cross-sectional study of over 3000 consecutive serum specimens the levels of rheumatoid fact... more In a cross-sectional study of over 3000 consecutive serum specimens the levels of rheumatoid factor (RF) measured by rate nephelometry (Beckman ICS II) were compared with values obtained by the more traditional methods of sheep cell agglutination (Rose-Waaler) and latex agglutination. Similar values for sensitivity and specificity were found for all three methods for rheumatoid arthritis, with nephelometry giving slightly higher levels of sensitivity for other rheumatic disorders. A significant correlation (r = 0.46, p less than 0.01) was found between the nephelometric and Rose-Waaler method for 147 consecutive seropositive specimens. Of interest, however, several disparate results were observed, and explanations for these were sought. Longitudinal studies of RF were performed in 49 seropositive patients over a two-year period. The nephelometric method was considered superior compared with the other techniques because of its ability to detect changes in absolute levels at earlier stages and its low interassay coefficient of variance (11%). We conclude that the nephelometric technique appears suitable for routine diagnostic use, offers several advantages compared with more traditional methods, and is no more expensive per test specimen than the Rose-Waaler technique.
To evaluate the role of low molecular weight (LMW) IgM and CD5 B cells in rheumatoid arthritis (R... more To evaluate the role of low molecular weight (LMW) IgM and CD5 B cells in rheumatoid arthritis (RA) and to explore the possibility that LMW IgM is derived selectively from this subset of B cells. LMW IgM in sera and culture supernatants was detected by a sensitive immunoblot technique with an enhanced chemiluminescence detection system. CD5 B cells were determined by FACScan cytometry. In vitro studies were established in culture plates containing pokeweed mitogen with or without 2-mercaptoethanol (2-ME). Supernatants were obtained from CD5 positive hybridomas and CD5 negative hybridomas. Other immunological indices were measured by laser nephelometry. Circulating LMW IgM was detected in all rheumatoid patients with significantly higher levels being observed in sero-positive patients. LMW IgM correlated significantly with total IgM and RF. Peripheral blood mononuclear cells (PBMC) from the majority of the patients with RA secreted LMW IgM in vitro as did mononuclear cells from a synovial fluid sample. The addition of low concentrations of 2-ME to the culture medium enhanced the proportions of secreted monomeric IgM. In contrast, PBMC from healthy subjects secreted only trace quantities of LMW IgM. In RA no significant correlations were observed between CD5 B cells and LMW IgM and RF. LMW IgM could be detected in the supernatants from both CD5+ and CD5- B cell lines. Finally, CD5 B cells were not significantly elevated in RA and levels remained constant over time. LMW IgM exists in high concentrations in RA sera and synovial fluid. Serum level correlates with RF and IgM. In vitro studies have suggested that the occurrence of LMW IgM may be due to an intrinsic defect(s) in the assembly of the IgM pentameric molecule. LMW IgM is unlikely to be derived solely from CD5 B cells.
To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well a... more To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well as their clinical associations, in a well-characterized Australian patient cohort. Serum from 505 Australian SSc patients were analyzed with a commercial line immunoassay (EuroLine; Euroimmun) for autoantibodies to centromere proteins CENP-A and CENP-B, RNA polymerase III (RNAP III; epitopes 11 and 155), the 90-kd nucleolar protein NOR-90, fibrillarin, Th/To, PM/Scl-75, PM/Scl-100, Ku, topoisomerase I (topo I), tripartite motif-containing protein 21/Ro 52, and platelet-derived growth factor receptor. Patient subgroups were identified by hierarchical clustering of the first 2 dimensions of a principal components analysis of quantitative autoantibody scores. Results were compared with detailed clinical data. A total of 449 of the 505 patients were positive for at least 1 autoantibody by immunoblotting. Heatmap visualization of autoantibody scores, along with principal components analysis clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP III, and topo I. Five patient clusters were identified: CENP, RNAP III strong, RNAP III weak, topo I, and other. Clinical features associated with CENP, RNAP III, and topo I were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP III into 2 clusters. Patients in the RNAP III strong cluster had an increased risk of gastric antral vascular ectasia, but a lower risk of esophageal dysmotility. Patients in the other cluster were more likely to be male and to have a history of smoking and a history of malignancy, but were less likely to have telangiectasia, Raynaud's phenomenon, and joint contractures. Five major autoantibody clusters with specific clinical and serologic associations were identified in Australian SSc patients. Subclassification and disease stratification using autoantibodies may have clinical utility, particularly in early disease.
Australian and New Zealand journal of medicine, 1999
The mitotic spindle apparatus (MSA) is a unique structure of microtubules and associated proteins... more The mitotic spindle apparatus (MSA) is a unique structure of microtubules and associated proteins involved in the segregation and reorganisation of chromosomes during cell division. Autoantibodies to the MSA (anti-MSA) are reported to occur rarely, but are easily identified during the immunofluorescent detection of anti-nuclear antibodies (ANA), and are generally reported as part of that investigation. As the clinical significance of these antibodies is unknown, our aim was to identify the clinical features of subjects identified with anti-MSA, and in a subset investigate the co-association with organ specific anti-thyroid antibodies. All ANA results from the three major immunology laboratories serving South Australia between January 1993 and June 1998 were retrospectively reviewed to identify anti-MSA subjects. Clinical details were extracted from hospital or general practice records using a standard proforma. Thyroid autoantibodies were measured using standard technique. A control...
Australian and New Zealand journal of medicine, 1996
The clinical associations of anti-lamin autoantibodies were first described in 1973. Since then a... more The clinical associations of anti-lamin autoantibodies were first described in 1973. Since then a number of individual case reports and two small series have been published. These have suggested an association with connective tissue disorders and autoimmune liver disease. To identify the clinical and laboratory associations of anti-lamin autoantibodies in an Australian population. Retrospective review of routine antinuclear antibody testing between 1990-1994 for characteristics linear staining of nuclear envelope on indirect immunofluorescence on HEp-2 cells with clinical status defined by retrospective review of case records. Twenty-eight patients were identified and the clinical status of 27 patients defined. Eleven patients had associated IgG anti-cardiolipin antibodies; anti-phospholipid syndrome was present in nine. Seven further patients had liver disease; five had autoimmune liver disease, with associated autoantibodies. The remaining nine patients had a diverse group of dise...
Previous studies have demonstrated an increased risk of breast cancer among patients with systemi... more Previous studies have demonstrated an increased risk of breast cancer among patients with systemic sclerosis (scleroderma). To describe the clinical characteristics of 21 patients with both systemic sclerosis and breast cancer, and compare their risk factors to female scleroderma patients without breast cancer, in a population-based cohort study of South Australia. Subjects with scleroderma and breast cancer were identified from the South Australian Scleroderma Register with cross-linking to the South Australian Cancer Registry, last updated to the end of December 2005. Clinical information was obtained from standardised self-administered questionnaires and case note reviews. Odds ratios for the risk factors for breast cancer in scleroderma were determined, and clinical variables were analysed using chi square, Fisher's exact, Mann-Whitney and t tests. At the end of December 2005 there were a total of 389 female patients with scleroderma. Of these, 21 (5.4%) had been diagnosed with breast cancer. The mean age of onset of scleroderma was 43.5 years, and the mean age of breast cancer was 60.5 years in those with scleroderma and breast cancer. The majority (71.4%) had limited scleroderma, with anti-centromere antibody being the most prevalent serological abnormality. In 16 (76%) patients the diagnosis of breast cancer occurred on an average of 22.3 years after the onset of their first scleroderma symptom. When compared to 48 controls, scleroderma patients with breast cancer were found to have a higher incidence of a positive family history of breast cancer (Fisher's exact test, p = 0.04) and a lower incidence of hormone-replacement therapy use (Fisher's exact test, p = 0.0026). This population-based cohort study provides evidence that the majority of patients with scleroderma and breast cancer have limited scleroderma and anti-centromere antibody. Given the increased incidence of solid tumours in systemic sclerosis, we suggest regular screening of female patients for breast cancer, especially in those with a family history.
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