Background. Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vacci... more Background. Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been recently shown to be impaired in kidney transplant recipients (KTRs), but the underlying factors affecting vaccine effectiveness need to be further elucidated. Methods. In this prospective cohort study, antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%) in 736 KTRs, who were previously either naive or infected with SARS-CoV-2 and vaccinated before or after transplantation. Cellular response was analyzed in a subset of patients using an interferon gamma release assay (cutoff 0.15 IU/mL, sensitivity 92%, and specificity 100%). Results. Seroconversion was significantly more impaired in SARS-CoV-2–naive KTRs than in those previously infected (40.1% versus 97.1%; P < 0.001). Mycophenolate use (odds ratio, 0.15; 95% confidence interval, 0.09-0.24; P < 0.001) and depleting therapy in the past year (odds ratio, 0.19; 95% confidence interval, 0.05-0.8; P = 0.023) were found to be among independent factors associated with impaired humoral response. Similarly, the interferon gamma release assay tested in 50 KTRs (cutoff 0.15 IU/mL, sensitivity 92%, specificity 100%) showed that specific T-cell responses against spike protein epitopes are impaired in SARS-CoV-2–naive KTRs, as compared to previously infected KTRs (9.4% versus 90%, P < 0.001). All 35 KTRs vaccinated on the waiting list before transplantation exhibited sustained seroconversion persisting after transplantation. Conclusions. Survivors of coronavirus disease 2019 and those vaccinated while on the waiting list exhibited a marked immune response to mRNA vaccines, contrary to poor response in naive KTRs vaccinated after transplantation (NCT04832841).
The multifunctional cytokine IL-6, which can be locally produced by human bronchial epithelial ce... more The multifunctional cytokine IL-6, which can be locally produced by human bronchial epithelial cells (HBECs), has been found to play a role in IL-4 dependent IgE synthesis. Since the allergic reaction in bronchial asthma is associated with the upregulation of IL-4 and Th2 type of immune response, the purpose of our study was to assess whether IL-4 and related cytokines IL-10 and IL-13 regulate IL-6 release by HBEC s. HBECs were obtained by bronchial brushing, cultured in LHC-9/RPMI 1640. At the third passage the cells were stimulated with cytokines (0.1-20 ng/ml) diluted in unsupplemented media for 24 h. The supernatants were tested for IL-6 content by sandwich ELISA. Unstimulated HBECs produced detectable amounts of IL-6 (368+/-25 pg/ml). Exposure to IL-10 (368+/-22 pg/ml) and IL-13 (395+/-6 pg/ml) resulted in little changes. IL-4 caused a slight but significant increase in IL-6 release (530+/-45 pg/ml), P<0.05, TNFalpha (1657+/-85 pg/ml) and IFNgamma (1953+/-37 pg/ml) showed strong induction of IL-6 release in HBECs (P<0.005 and P<0.001, respectively). Both IL-4 and IL-13 significantly inhibited TNF induced IL-6 release (P<0.01 for both) while augmenting the effect of IFNgamma (P<0.005 and P<0.01, respectively.). IL-10 was without a significant effect. We conclude that Th2-type cytokines IL-4 and IL-13 affect the release of IL-6 by HBECs in response to TNFalpha (inhibition) and IFgamma (augmentation). IL-10 had no effect on the regulation of IL-6 release. Modulation of IL-6 levels by Th2-type cytokines may play a role in allergic reactions through the IL-6 promoting effect on IL-4 mediated IgE production.
Introduction: Idiopathic pulmonary fibrosis (IPF) is a serious disease with unknown etiology, whe... more Introduction: Idiopathic pulmonary fibrosis (IPF) is a serious disease with unknown etiology, where an influence of cytokine gene polymorphisms is presumed. We compared HRCT alveolar (AS) and interstitial score (IS) and histoptahologic score with IL-4, and IL-4RA gene polymorphisms in IPF patients. Subjects and methods: IPF was diagnosed in 46 patients according to ATS/ERS consensus statement. 43 patients had evaluable HRCT investigations, 14 patients had surgical lung biopsy. HRCT scans were evaluated using IS and AS scales by Gay et al. The histopathological evaluation of lung biopsies comprised: myofibroblast foci (MF), inflammation, eosinophils, granulomas and Ashcroft criteria for fibrosis grading. The IL-4 (-1098) (-590) (-33) and IL-4 RA +1902 gene polymorphisms were characterized utilizing a PCR- SSP method. Results: AS was higher in IL-4 haplotypes 1 TTC and TTT carrierrs (p=0.0423). Ashcroft score was more advanced in IL-4 haplotype 2 GCC (p= 0,013) and MF counts were higher in TCC carriers (p=0,0736). IL-4 RA +1902 A1 G and IL-4 -590 A1 T correlated with higher AS (p=0,0335; p=0,0123). Ashcroft score was higher in IL-4 -1098 A2 G and IL-4 -33 A1 T carriers (p= 0,0443, p=0,0915). Conclusions: We assume that IL-4 and IL-4RA polymorphisms might influence HRCT and histopathological phenotype of IPF. The correlation of functionally relevant IL-4 genes polymorphisms (especially IL-4 -33 T) with AS could mean, that new alveolar lesions with continuing fibrosis are more pronounced in these polymorphisms carriers. The positive correlation of IL-4 -33 A1 T with Ashcroft score might support a hypothesis of fibrogenetic role of IL-4 in IPF.
Objectives: MRP8/14 is a heterodimer of two myeloid calcium-binding proteins associated with diff... more Objectives: MRP8/14 is a heterodimer of two myeloid calcium-binding proteins associated with different types of acute inflammatory processes. We studied MRP8/14 together with procalcitonin (PCT) serum levels in order to diagnose infectious complications or the rejection process affecting kidney or heart allograft. Methods: A total of 419 serum samples was evaluated. MRP8/14 levels were measured by ELISA (BMA Biomed), PCT by a sensitive immunoluminiscent assay ILMA (Brahms Diagn.) Results: Both parameters showed very low basal levels in healthy subjects (range 303-1,660 ng/ml of MRP8/14; less than 0.08 ng/ml of PCT). A rapid increase in serum levels occurred in response to bacterial infections (MRP8/14 up to 6,230 ng/ml; PCT up to 297 ng/ml). Serum PCT concentration remained low in the presence of kidney allograft rejection, where MRP8/14 levels were increased. An uncomplicated outcome of kidney or heart transplantation did not change basal serum MRP8/14 and PCT levels. Conclusions: We conclude that 1) both MRP8/14 and PCT are very sensitive markers of complications in organ transplant recipients (normal values in uncomplicated outcome) 2) combination of both parameters is useful to discriminate between rejection (increased MRP8/14 with normal PCT) and systemic bacterial infection (both parameters increased).
American Journal of Physiology-lung Cellular and Molecular Physiology, Sep 1, 1997
The airway epithelial cell may play a role as an effector cell, releasing various cytokines and e... more The airway epithelial cell may play a role as an effector cell, releasing various cytokines and extracellular matrix components in immune responses, inflammation, and wound repair processes, thus contributing to cytokine "networks." The cytokines transforming growth factor (TGF)-beta and interleukin (IL)-4 are though to have pivotal roles in airway diseases, with IL-4 having proinflammatory actions and TGF-beta generally regarded to mediate repair and to attenuate immune responses. In asthma, where IL-4 and TGF-beta are thought to contribute to the inflammatory process and repair, respectively, interactions between these cytokines are likely to be of importance. Therefore, we studied the potential interaction of both cytokines by measuring IL-8 and fibronectin release by cultured human bronchial epithelial cells (HBECs). IL-4 is capable of inducing IL-8 release from HBECs. This effect of IL-4 can be blocked by the concurrent presence of the cytokine TGF-beta. In contrast, TGF-beta had a modest inconsistent stimulatory effect on IL-8 release by itself and had no effect on the IL-8 release induced by tumor necrosis factor (TNF)-alpha. An antagonistic effect of IL-4 and TGF-beta was also observed on HBEC fibronectin release. TGF-beta stimulated fibronectin release, and IL-4 was able to inhibit this. This effect was not due to a redistribution of fibronectin but appeared to be due to a true reduction in synthesis. Consistent with this, IL-4 and TGF-beta effects on IL-8 and fibronectin release were paralleled by changes in mRNA levels. The ability of TGF-beta to block IL-4-induced IL-8 release is certainly not the only mechanism to inhibit IL-8 release because dexamethasone was capable of inhibiting both TNF-alpha- and IL-4-induced release of IL-8. These results indicate that TGF-beta and IL-4 can have mutually inhibitory effects. The balance determined by this reciprocal inhibition may play an important role in regulating inflammation repair and in diseases such as asthma.
Radiation exposure is known to impair healing in irradiated areas. Fibroblasts play a major role ... more Radiation exposure is known to impair healing in irradiated areas. Fibroblasts play a major role in the production and modification of extracellular matrix in wound repair. Since one important aspect of wound repair is the contraction of the wound, this study investigated the effects of radiation on the ability of fibroblasts to mediate collagen gel contraction in an in vitro model of wound retraction. After irradiation, the cells were detached and suspended in a solution of rat tail tendon collagen. Radiation exposure decreased retraction, and this effect was dose dependent. In order to define the mechanism of reduced gel retraction, we investigated alpha2beta1 cell surface integrin and fibronectin, which are thought to mediate contraction, and prostaglandin E2 (PGE2), which is known to inhibit this process. PGE2 release increased dose responsively following radiation. The cyclooxygenase inhibitor indomethacin could partially restore the contractile activity of irradiated fibroblasts. Fibronectin production in gel culture showed a significant decrease. In contrast, there was no decrease in alpha2beta1 integrin expression in radiated cells. In conclusion, radiation decreases fibroblast-mediated gel contraction. Increased PGE2 production and decreased fibronectin production by irradiated fibroblasts may contribute to this effect and may be in part responsible for poor healing of radiated tissue.
Procalcitonin (PCT) represents a new marker of systemic inflammatory reactions of the body to inf... more Procalcitonin (PCT) represents a new marker of systemic inflammatory reactions of the body to infections. PCT is selectively induced by severe bacterial infections leading to sepsis or multiorgan dysfunction syndrome. The aim of our study was to test PCT as a postoperative infection marker in heart and kidney transplant patients compared with healthy subjects and patients with localized lung-inflammatory processes without a manifest systemic response. PCT concentrations were measured by an immunoluminometric assay (ILMA) in a total of 419 serum samples. Normal serum levels were in the range of 0.08-0.6 ng/ml. Operative trauma associated with heart (not kidney) transplantation induced a transient increase in PCT levels to 7-10 ng/ml with a decline to normal levels within 2-3 days in most patients. Severe bacterial infections dramatically augmented serum PCT concentrations reaching values of 46-297 ng/ml in the most critical periods. Good response to antibiotic therapy was associated with a decline in serum PCT concentrations. Acute rejection or cytomegalovirus infections did not significantly increase the serum PCT levels. Localized pulmonary infections showed either no, or only a limited increase, in the serum PCT levels (max. 7 ng/ml). We conclude from our data that PCT can be used as a sensitive marker to differentiate systemic bacterial infections from other complications in organ transplantation.
Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term ren... more Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term renal graft loss. TGF-beta1 is a key profibrogenic cytokine associated with CAN pathogenesis. Because of clinical diagnostic inaccuracy, protocol biopsy has been suggested to be a beneficial method for early CAN detection. Protocol core biopsy was carried out in 67 consecutive cyclosporine-based immunosuppression-treated kidney transplant recipients with stable renal function 12 months after renal transplantation. Biopsy specimens were analyzed morphologically according to Banff-97' criteria and immunohistologically for TGF-beta1 staining. The data obtained were correlated with plasma TGF-beta1 levels and clinical data. CAN (grade I-III) was found in 51 patients (76 %). CAN grade I was found to be the most frequent one (44 %). A normal finding within the graft was made in only 12 patients (18 %). Clinically silent acute rejection Banff IA was present in 4 patients (6 %). In 8 patients (...
Purpose Advanced age is associated with an impaired humoral immune response to SARS-CoV-2 mRNA va... more Purpose Advanced age is associated with an impaired humoral immune response to SARS-CoV-2 mRNA vaccination in kidney transplant recipients (KTR). The mechanisms are, however, poorly understood. Frailty syndrome assessment may determine the most vulnerable population. Methods This study is a secondary analysis of a prospective study (NCT04832841) regarding seroconversion after BNT162b2 vaccination, including 101 SARS-CoV-2 naïve KTR 70 years and older. The Fried frailty components were evaluated, and antibodies against S1 and S2 subunits of SARS-CoV-2 were examined > 14 days after the second dose of BNT162b2 vaccine. Results Seroconversion was observed in 33 KTR. Male gender, eGFR, MMF-free immunosuppression, and a lower frailty score were associated with higher seroconversion rates in univariable regression. Concerning frailty components, physical inactivity had the most negative effect on seroconversion (OR = 0.36, 95% CI 0.14–0.95, p = 0.039). In a multivariable regression adju...
Background. Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vacci... more Background. Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been recently shown to be impaired in kidney transplant recipients (KTRs), but the underlying factors affecting vaccine effectiveness need to be further elucidated. Methods. In this prospective cohort study, antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%) in 736 KTRs, who were previously either naive or infected with SARS-CoV-2 and vaccinated before or after transplantation. Cellular response was analyzed in a subset of patients using an interferon gamma release assay (cutoff 0.15 IU/mL, sensitivity 92%, and specificity 100%). Results. Seroconversion was significantly more impaired in SARS-CoV-2–naive KTRs than in those previously infected (40.1% versus 97.1%; P < 0.001). Mycophenolate use (odds ratio, 0.15; 95% confidence interval, 0.09-0.24; P < 0.001) and depleting therapy in the past year (odds ratio, 0.19; 95% confidence interval, 0.05-0.8; P = 0.023) were found to be among independent factors associated with impaired humoral response. Similarly, the interferon gamma release assay tested in 50 KTRs (cutoff 0.15 IU/mL, sensitivity 92%, specificity 100%) showed that specific T-cell responses against spike protein epitopes are impaired in SARS-CoV-2–naive KTRs, as compared to previously infected KTRs (9.4% versus 90%, P < 0.001). All 35 KTRs vaccinated on the waiting list before transplantation exhibited sustained seroconversion persisting after transplantation. Conclusions. Survivors of coronavirus disease 2019 and those vaccinated while on the waiting list exhibited a marked immune response to mRNA vaccines, contrary to poor response in naive KTRs vaccinated after transplantation (NCT04832841).
The multifunctional cytokine IL-6, which can be locally produced by human bronchial epithelial ce... more The multifunctional cytokine IL-6, which can be locally produced by human bronchial epithelial cells (HBECs), has been found to play a role in IL-4 dependent IgE synthesis. Since the allergic reaction in bronchial asthma is associated with the upregulation of IL-4 and Th2 type of immune response, the purpose of our study was to assess whether IL-4 and related cytokines IL-10 and IL-13 regulate IL-6 release by HBEC s. HBECs were obtained by bronchial brushing, cultured in LHC-9/RPMI 1640. At the third passage the cells were stimulated with cytokines (0.1-20 ng/ml) diluted in unsupplemented media for 24 h. The supernatants were tested for IL-6 content by sandwich ELISA. Unstimulated HBECs produced detectable amounts of IL-6 (368+/-25 pg/ml). Exposure to IL-10 (368+/-22 pg/ml) and IL-13 (395+/-6 pg/ml) resulted in little changes. IL-4 caused a slight but significant increase in IL-6 release (530+/-45 pg/ml), P<0.05, TNFalpha (1657+/-85 pg/ml) and IFNgamma (1953+/-37 pg/ml) showed strong induction of IL-6 release in HBECs (P<0.005 and P<0.001, respectively). Both IL-4 and IL-13 significantly inhibited TNF induced IL-6 release (P<0.01 for both) while augmenting the effect of IFNgamma (P<0.005 and P<0.01, respectively.). IL-10 was without a significant effect. We conclude that Th2-type cytokines IL-4 and IL-13 affect the release of IL-6 by HBECs in response to TNFalpha (inhibition) and IFgamma (augmentation). IL-10 had no effect on the regulation of IL-6 release. Modulation of IL-6 levels by Th2-type cytokines may play a role in allergic reactions through the IL-6 promoting effect on IL-4 mediated IgE production.
Introduction: Idiopathic pulmonary fibrosis (IPF) is a serious disease with unknown etiology, whe... more Introduction: Idiopathic pulmonary fibrosis (IPF) is a serious disease with unknown etiology, where an influence of cytokine gene polymorphisms is presumed. We compared HRCT alveolar (AS) and interstitial score (IS) and histoptahologic score with IL-4, and IL-4RA gene polymorphisms in IPF patients. Subjects and methods: IPF was diagnosed in 46 patients according to ATS/ERS consensus statement. 43 patients had evaluable HRCT investigations, 14 patients had surgical lung biopsy. HRCT scans were evaluated using IS and AS scales by Gay et al. The histopathological evaluation of lung biopsies comprised: myofibroblast foci (MF), inflammation, eosinophils, granulomas and Ashcroft criteria for fibrosis grading. The IL-4 (-1098) (-590) (-33) and IL-4 RA +1902 gene polymorphisms were characterized utilizing a PCR- SSP method. Results: AS was higher in IL-4 haplotypes 1 TTC and TTT carrierrs (p=0.0423). Ashcroft score was more advanced in IL-4 haplotype 2 GCC (p= 0,013) and MF counts were higher in TCC carriers (p=0,0736). IL-4 RA +1902 A1 G and IL-4 -590 A1 T correlated with higher AS (p=0,0335; p=0,0123). Ashcroft score was higher in IL-4 -1098 A2 G and IL-4 -33 A1 T carriers (p= 0,0443, p=0,0915). Conclusions: We assume that IL-4 and IL-4RA polymorphisms might influence HRCT and histopathological phenotype of IPF. The correlation of functionally relevant IL-4 genes polymorphisms (especially IL-4 -33 T) with AS could mean, that new alveolar lesions with continuing fibrosis are more pronounced in these polymorphisms carriers. The positive correlation of IL-4 -33 A1 T with Ashcroft score might support a hypothesis of fibrogenetic role of IL-4 in IPF.
Objectives: MRP8/14 is a heterodimer of two myeloid calcium-binding proteins associated with diff... more Objectives: MRP8/14 is a heterodimer of two myeloid calcium-binding proteins associated with different types of acute inflammatory processes. We studied MRP8/14 together with procalcitonin (PCT) serum levels in order to diagnose infectious complications or the rejection process affecting kidney or heart allograft. Methods: A total of 419 serum samples was evaluated. MRP8/14 levels were measured by ELISA (BMA Biomed), PCT by a sensitive immunoluminiscent assay ILMA (Brahms Diagn.) Results: Both parameters showed very low basal levels in healthy subjects (range 303-1,660 ng/ml of MRP8/14; less than 0.08 ng/ml of PCT). A rapid increase in serum levels occurred in response to bacterial infections (MRP8/14 up to 6,230 ng/ml; PCT up to 297 ng/ml). Serum PCT concentration remained low in the presence of kidney allograft rejection, where MRP8/14 levels were increased. An uncomplicated outcome of kidney or heart transplantation did not change basal serum MRP8/14 and PCT levels. Conclusions: We conclude that 1) both MRP8/14 and PCT are very sensitive markers of complications in organ transplant recipients (normal values in uncomplicated outcome) 2) combination of both parameters is useful to discriminate between rejection (increased MRP8/14 with normal PCT) and systemic bacterial infection (both parameters increased).
American Journal of Physiology-lung Cellular and Molecular Physiology, Sep 1, 1997
The airway epithelial cell may play a role as an effector cell, releasing various cytokines and e... more The airway epithelial cell may play a role as an effector cell, releasing various cytokines and extracellular matrix components in immune responses, inflammation, and wound repair processes, thus contributing to cytokine "networks." The cytokines transforming growth factor (TGF)-beta and interleukin (IL)-4 are though to have pivotal roles in airway diseases, with IL-4 having proinflammatory actions and TGF-beta generally regarded to mediate repair and to attenuate immune responses. In asthma, where IL-4 and TGF-beta are thought to contribute to the inflammatory process and repair, respectively, interactions between these cytokines are likely to be of importance. Therefore, we studied the potential interaction of both cytokines by measuring IL-8 and fibronectin release by cultured human bronchial epithelial cells (HBECs). IL-4 is capable of inducing IL-8 release from HBECs. This effect of IL-4 can be blocked by the concurrent presence of the cytokine TGF-beta. In contrast, TGF-beta had a modest inconsistent stimulatory effect on IL-8 release by itself and had no effect on the IL-8 release induced by tumor necrosis factor (TNF)-alpha. An antagonistic effect of IL-4 and TGF-beta was also observed on HBEC fibronectin release. TGF-beta stimulated fibronectin release, and IL-4 was able to inhibit this. This effect was not due to a redistribution of fibronectin but appeared to be due to a true reduction in synthesis. Consistent with this, IL-4 and TGF-beta effects on IL-8 and fibronectin release were paralleled by changes in mRNA levels. The ability of TGF-beta to block IL-4-induced IL-8 release is certainly not the only mechanism to inhibit IL-8 release because dexamethasone was capable of inhibiting both TNF-alpha- and IL-4-induced release of IL-8. These results indicate that TGF-beta and IL-4 can have mutually inhibitory effects. The balance determined by this reciprocal inhibition may play an important role in regulating inflammation repair and in diseases such as asthma.
Radiation exposure is known to impair healing in irradiated areas. Fibroblasts play a major role ... more Radiation exposure is known to impair healing in irradiated areas. Fibroblasts play a major role in the production and modification of extracellular matrix in wound repair. Since one important aspect of wound repair is the contraction of the wound, this study investigated the effects of radiation on the ability of fibroblasts to mediate collagen gel contraction in an in vitro model of wound retraction. After irradiation, the cells were detached and suspended in a solution of rat tail tendon collagen. Radiation exposure decreased retraction, and this effect was dose dependent. In order to define the mechanism of reduced gel retraction, we investigated alpha2beta1 cell surface integrin and fibronectin, which are thought to mediate contraction, and prostaglandin E2 (PGE2), which is known to inhibit this process. PGE2 release increased dose responsively following radiation. The cyclooxygenase inhibitor indomethacin could partially restore the contractile activity of irradiated fibroblasts. Fibronectin production in gel culture showed a significant decrease. In contrast, there was no decrease in alpha2beta1 integrin expression in radiated cells. In conclusion, radiation decreases fibroblast-mediated gel contraction. Increased PGE2 production and decreased fibronectin production by irradiated fibroblasts may contribute to this effect and may be in part responsible for poor healing of radiated tissue.
Procalcitonin (PCT) represents a new marker of systemic inflammatory reactions of the body to inf... more Procalcitonin (PCT) represents a new marker of systemic inflammatory reactions of the body to infections. PCT is selectively induced by severe bacterial infections leading to sepsis or multiorgan dysfunction syndrome. The aim of our study was to test PCT as a postoperative infection marker in heart and kidney transplant patients compared with healthy subjects and patients with localized lung-inflammatory processes without a manifest systemic response. PCT concentrations were measured by an immunoluminometric assay (ILMA) in a total of 419 serum samples. Normal serum levels were in the range of 0.08-0.6 ng/ml. Operative trauma associated with heart (not kidney) transplantation induced a transient increase in PCT levels to 7-10 ng/ml with a decline to normal levels within 2-3 days in most patients. Severe bacterial infections dramatically augmented serum PCT concentrations reaching values of 46-297 ng/ml in the most critical periods. Good response to antibiotic therapy was associated with a decline in serum PCT concentrations. Acute rejection or cytomegalovirus infections did not significantly increase the serum PCT levels. Localized pulmonary infections showed either no, or only a limited increase, in the serum PCT levels (max. 7 ng/ml). We conclude from our data that PCT can be used as a sensitive marker to differentiate systemic bacterial infections from other complications in organ transplantation.
Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term ren... more Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term renal graft loss. TGF-beta1 is a key profibrogenic cytokine associated with CAN pathogenesis. Because of clinical diagnostic inaccuracy, protocol biopsy has been suggested to be a beneficial method for early CAN detection. Protocol core biopsy was carried out in 67 consecutive cyclosporine-based immunosuppression-treated kidney transplant recipients with stable renal function 12 months after renal transplantation. Biopsy specimens were analyzed morphologically according to Banff-97' criteria and immunohistologically for TGF-beta1 staining. The data obtained were correlated with plasma TGF-beta1 levels and clinical data. CAN (grade I-III) was found in 51 patients (76 %). CAN grade I was found to be the most frequent one (44 %). A normal finding within the graft was made in only 12 patients (18 %). Clinically silent acute rejection Banff IA was present in 4 patients (6 %). In 8 patients (...
Purpose Advanced age is associated with an impaired humoral immune response to SARS-CoV-2 mRNA va... more Purpose Advanced age is associated with an impaired humoral immune response to SARS-CoV-2 mRNA vaccination in kidney transplant recipients (KTR). The mechanisms are, however, poorly understood. Frailty syndrome assessment may determine the most vulnerable population. Methods This study is a secondary analysis of a prospective study (NCT04832841) regarding seroconversion after BNT162b2 vaccination, including 101 SARS-CoV-2 naïve KTR 70 years and older. The Fried frailty components were evaluated, and antibodies against S1 and S2 subunits of SARS-CoV-2 were examined > 14 days after the second dose of BNT162b2 vaccine. Results Seroconversion was observed in 33 KTR. Male gender, eGFR, MMF-free immunosuppression, and a lower frailty score were associated with higher seroconversion rates in univariable regression. Concerning frailty components, physical inactivity had the most negative effect on seroconversion (OR = 0.36, 95% CI 0.14–0.95, p = 0.039). In a multivariable regression adju...
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