HLA phenotypes of 66 parents of 33 infants succumbing to the sudden infant death syndrome (SIDS) ... more HLA phenotypes of 66 parents of 33 infants succumbing to the sudden infant death syndrome (SIDS) were determined using a standard microlymphocytotoxicity method. Heterogeneity testing over all locus antigens revealed a significant difference between the parents and a control group consisting of blood donors and healthy unrelated volunteers. This heterogeneity was still evident when maternal and paternal groups were considered separately with the controls and when compared with each other. Individual A locus antigens displaying frequency deviation from control values included A9 (decreased in husbands), A10 (increased in wives and total parent group), and A28 (increased in wives). The increase in frequency of A10 became highly significant when only parents of children with evidence of laryngitis at post mortem were used for comparison with control values. No difference in B locus antigens between any of the groups was observed. The results obtained are compatible with the view that SIDS is the result of a hypersensitivity reaction to one or more allergens and that genes coding for these specific responses are linked to the HLA complex. Differences observed between the maternal and paternal groups may be explained on the basis of maternal antibody, passively acquired by the infant, which serves a protective role in the respiratory tract, prior to the development of immunocompetence. The production of these antibodies is also dependent on genes linked to the maternal HLA complex.
The leukocyte migration test was used to detect cellular immunity to HL-A antigens present on the... more The leukocyte migration test was used to detect cellular immunity to HL-A antigens present on the husband's lymphocytes and spermatozoa in a group of fertile and infertile couples. Approximately 50% of the married female population appear to be sensitized. There was no difference between the fertile and infertile groups in the frequency of positive results, but a greater number of migration indices were below 0.7 and 0.6 in the infertile group. It is suggested that sperm cells are the most likely cause of immunization.
In 43 cases of chronic active hepatitis of autoimmune-type, HLA-D locus-related antigens (HLA-DR)... more In 43 cases of chronic active hepatitis of autoimmune-type, HLA-D locus-related antigens (HLA-DR) as well as A and B locus antigens were typed serologically. For 14 patients carrying HLA-B8 and DRw3 family members were typed to establish haplotypes. Control groups consisted of healthy persons and patients with chronic liver disease unrelated to autoimmune CAH (alcoholic cirrhosis and cryptogenic cirrhosis). In autoimmune CAH, DRw3 was significantly increased, 74%, compared with healthy controls, 32%, and liver controls, 31%, this increase being similar to the increase of HLA-B8. There was marked co-occurrence of HLA-B8 and DRw3 in 31 of 33 individuals positive for either antigen. DRw3 was present in 23 of the 24 cases with disease-onset before age 30 hr. HLA typing on the 14 families showed that a haplotype including B8 and DRw3 was present in all index patients; this haplotype also included A1 in 10 cases, A9 in 2 cases, and A2 and A28 in 1 case. The results indicate that in the autoimmune type of chronic active hepatitis occurring characteristically in young females, there exists a disease susceptibility gene strongly associated with the B and D locus of the major histocompatibility complex (MHC), and acting in concert with other non-MHC gene loci and/or environmental factors.
Genetic determinants of the autoimmune type of chronic active hepatitis include the major histoco... more Genetic determinants of the autoimmune type of chronic active hepatitis include the major histocompatibility complex alleles HLA-B8 and HLA-DR3, which are usually present as the haplotype A1, B8, DR3. In certain other autoimmune diseases, an extended haplotype including complement alleles confers a greater relative risk than does B8, DR3. Hence, extended haplotypes were ascertained in autoimmune chronic active hepatitis by typing for HLA, complement alleles C4A, C4B, and Bf, and glyoxalase type 1 or 2. Eight of the 10 B8, DR3 haplotypes were A1, B8, DR3. Of the 8, 7 had the extended haplotype A1, B8, C4AQ0, C4B1, BfS, DR3, but this haplotype occurred in four instances with glyoxalase 2 and in three with glyoxalase 1. Thus, we find that in autoimmune chronic active hepatitis there is a high frequency of null alleles for complement but an extended haplotype does not cause any greater risk for disease than B8, DR3 alone.
One hundred and twelve hospital based outpatients with rheumatoid arthritis (mean duration +/- st... more One hundred and twelve hospital based outpatients with rheumatoid arthritis (mean duration +/- standard error, 10.7 +/- 0.9 years) were studied for radiological progression of the hands and wrists over a mean period of 26.5 +/- 0.5 months. The majority were taking slow acting antirheumatic drugs (SAARD). The rate of radiographic progression was positively and independently associated with the female sex (p less than 0.01), erythrocyte sedimentation rate (ESR, p less than 0.05) and HLA-DR1 (p less than 0.05). There was a negative association with HLA-DR4 (p less than 0.05) but this was no longer significant after adjusting for ESR. There was no relationship between the rate of radiological progression and the presence of rheumatoid factor, rheumatoid nodules and duration of treatment with SAARD.
HLA phenotypes of 66 parents of 33 infants succumbing to the sudden infant death syndrome (SIDS) ... more HLA phenotypes of 66 parents of 33 infants succumbing to the sudden infant death syndrome (SIDS) were determined using a standard microlymphocytotoxicity method. Heterogeneity testing over all locus antigens revealed a significant difference between the parents and a control group consisting of blood donors and healthy unrelated volunteers. This heterogeneity was still evident when maternal and paternal groups were considered separately with the controls and when compared with each other. Individual A locus antigens displaying frequency deviation from control values included A9 (decreased in husbands), A10 (increased in wives and total parent group), and A28 (increased in wives). The increase in frequency of A10 became highly significant when only parents of children with evidence of laryngitis at post mortem were used for comparison with control values. No difference in B locus antigens between any of the groups was observed. The results obtained are compatible with the view that SIDS is the result of a hypersensitivity reaction to one or more allergens and that genes coding for these specific responses are linked to the HLA complex. Differences observed between the maternal and paternal groups may be explained on the basis of maternal antibody, passively acquired by the infant, which serves a protective role in the respiratory tract, prior to the development of immunocompetence. The production of these antibodies is also dependent on genes linked to the maternal HLA complex.
The leukocyte migration test was used to detect cellular immunity to HL-A antigens present on the... more The leukocyte migration test was used to detect cellular immunity to HL-A antigens present on the husband's lymphocytes and spermatozoa in a group of fertile and infertile couples. Approximately 50% of the married female population appear to be sensitized. There was no difference between the fertile and infertile groups in the frequency of positive results, but a greater number of migration indices were below 0.7 and 0.6 in the infertile group. It is suggested that sperm cells are the most likely cause of immunization.
In 43 cases of chronic active hepatitis of autoimmune-type, HLA-D locus-related antigens (HLA-DR)... more In 43 cases of chronic active hepatitis of autoimmune-type, HLA-D locus-related antigens (HLA-DR) as well as A and B locus antigens were typed serologically. For 14 patients carrying HLA-B8 and DRw3 family members were typed to establish haplotypes. Control groups consisted of healthy persons and patients with chronic liver disease unrelated to autoimmune CAH (alcoholic cirrhosis and cryptogenic cirrhosis). In autoimmune CAH, DRw3 was significantly increased, 74%, compared with healthy controls, 32%, and liver controls, 31%, this increase being similar to the increase of HLA-B8. There was marked co-occurrence of HLA-B8 and DRw3 in 31 of 33 individuals positive for either antigen. DRw3 was present in 23 of the 24 cases with disease-onset before age 30 hr. HLA typing on the 14 families showed that a haplotype including B8 and DRw3 was present in all index patients; this haplotype also included A1 in 10 cases, A9 in 2 cases, and A2 and A28 in 1 case. The results indicate that in the autoimmune type of chronic active hepatitis occurring characteristically in young females, there exists a disease susceptibility gene strongly associated with the B and D locus of the major histocompatibility complex (MHC), and acting in concert with other non-MHC gene loci and/or environmental factors.
Genetic determinants of the autoimmune type of chronic active hepatitis include the major histoco... more Genetic determinants of the autoimmune type of chronic active hepatitis include the major histocompatibility complex alleles HLA-B8 and HLA-DR3, which are usually present as the haplotype A1, B8, DR3. In certain other autoimmune diseases, an extended haplotype including complement alleles confers a greater relative risk than does B8, DR3. Hence, extended haplotypes were ascertained in autoimmune chronic active hepatitis by typing for HLA, complement alleles C4A, C4B, and Bf, and glyoxalase type 1 or 2. Eight of the 10 B8, DR3 haplotypes were A1, B8, DR3. Of the 8, 7 had the extended haplotype A1, B8, C4AQ0, C4B1, BfS, DR3, but this haplotype occurred in four instances with glyoxalase 2 and in three with glyoxalase 1. Thus, we find that in autoimmune chronic active hepatitis there is a high frequency of null alleles for complement but an extended haplotype does not cause any greater risk for disease than B8, DR3 alone.
One hundred and twelve hospital based outpatients with rheumatoid arthritis (mean duration +/- st... more One hundred and twelve hospital based outpatients with rheumatoid arthritis (mean duration +/- standard error, 10.7 +/- 0.9 years) were studied for radiological progression of the hands and wrists over a mean period of 26.5 +/- 0.5 months. The majority were taking slow acting antirheumatic drugs (SAARD). The rate of radiographic progression was positively and independently associated with the female sex (p less than 0.01), erythrocyte sedimentation rate (ESR, p less than 0.05) and HLA-DR1 (p less than 0.05). There was a negative association with HLA-DR4 (p less than 0.05) but this was no longer significant after adjusting for ESR. There was no relationship between the rate of radiological progression and the presence of rheumatoid factor, rheumatoid nodules and duration of treatment with SAARD.
Uploads