Summary
T lymphocyte hyperactivity and progressive inflammation in systemic lupus erythematosus (SLE) patients results in over‐expression of human leucocyte antigen (HLA)‐Ib on the surface of ...lymphocytes. These are shed into the circulation upon inflammation, and may augment production of antibodies promoting pathogenicity of the disease. The objective was to evaluate the association of HLA‐Ib (HLA‐E, HLA‐F and HLA‐G) antibodies to the disease activity of SLE. The immunoglobulin (Ig)G/IgM reactivity to HLA‐Ib and β2m in the sera of 69 German, 29 Mexican female SLE patients and 17 German female controls was measured by multiplex Luminex®‐based flow cytometry. The values were expressed as mean florescence intensity (MFI). Only the German SLE cohort was analysed in relation to the clinical disease activity. In the controls, anti‐HLA‐G IgG predominated over other HLA‐Ib antibodies, whereas SLE patients had a preponderance of anti‐HLA‐F IgG over the other HLA‐Ib antibodies. The disease activity index, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)‐2000, was reflected only in the levels of anti‐HLA‐F IgG. Anti‐HLA‐F IgG with MFI level of 500–1999 was associated with active SLE, whereas inactive SLE revealed higher MFI (>2000). When anti‐HLA‐F IgG were cross‐reactive with other HLA‐Ib alleles, their reactivity was reflected in the levels of anti‐HLA‐E and ‐G IgG. The prevalence of HLA‐F‐monospecific antibodies in SLE patients was also associated with the clinical disease activity. Anti‐HLA‐F IgG is possibly involved in the clearance of HLA‐F shed from lymphocytes and inflamed tissues to lessen the disease's severity, and thus emerges as a beneficial immune biomarker. Therefore, anti‐HLA‐Ib IgG should be considered as a biomarker in standard SLE diagnostics.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Sensitization to HLA antigens creates an obstacle for the accessibility and success of kidney transplantation (KT). Highly sensitized patients have longer waiting times and some may never ...receive a KT. Aim To determine the probability of patients on the deceased donor (DD) waiting list to receive a KT based on the panel reactive antibody percentage (% PRA) in our center. Methods The DD waiting list from our institution was analyzed from 01/05 to 08/12 documenting the clinical variables from donor and potential recipients (ABO blood group), lymphocyte cross-match CxM (CDC-AHG) results, highest % PRA determination, and time on the waiting list. The patients were classified into 4 groups based on the % PRA: 0%, 1–19%, 20–79% and 80–100%. The data was analyzed using odds ratio and logistic regression (significant p < 0.05). Results 58 DD (F:M 34:24, ABO group O = 35, A = 13, B = 10) and 179 potential recipients were analyzed (F:M 98:81, ABO group O = 127, A = 33, B = 19, participating 4.2 ± 3.8 times with different donors to receive KT). The mean PRA for the whole group was 22 ± 32%, median md 0 (0–98). A total of 100 patients received KT (mean waiting time 2.2 ± 1.7 years, 12 days–7 years) and their mean % PRA was 11.6 ± 24, md 0 (0–94) vs. 31.4 ± 37 md 8.5 (0–98) in those who have not received a KT. An association between the % PRA group and KT (p < 0.003) was observed. The probability of receiving KT with a 0% PRA vs. > 0% was higher (OR 2.12, 1.17–3.84). There was no difference between the 0% vs. 1–19% group (OR 1); differences were observed between 0% vs. 20–79% (OR 2.5, 1.18–5.3) and 0% vs. 80–100% (OR 5, 1.67–14.9). For every percent increase in the PRA above 20%, the risk of not receiving a KT increased by 5% (1–9, p < 0.01). Conclusions The probability of receiving a DD kidney transplant is inversely related to the % PRA although a higher risk for not receiving a KT becomes evident with a PRA > 20%.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Kidney transplant for patients with lupus nephritis (LN) has satisfactory outcomes in studies with short-term or mid-term follow up. Nevertheless, information about long-term outcomes is scarce. We ...performed a retrospective matched-pair cohort study in 74 LN recipients compared with 148 non-LN controls matched by age, sex, immunosuppressive treatment, human leukocyte antigen (HLA) matches, and transplant period in order to evaluate long-term outcomes of kidney transplant in LN recipients. Matched pairs were predominantly females (83%), median age at transplant surgery of 32 years (interquartile range 23–38 years), and 66% received a graft from a living related donor. Among LN recipients, 5-, 10-, 15-, and 20-year graft survival was 81%, 79%, 57% and 51%, respectively, and it was similar to that observed in controls (89%, 78%, 64%, and 56%, respectively). Graft loss (27% vs. 21%, p = 0.24) and overall survival (p = 0.15) were not different between LN recipients and controls. Also, there was no difference in episodes of immunological rejection, thrombosis, or infection. Only six LN recipients had biopsy-proven lupus recurrence and three of them had graft loss. In a cohort with a long follow up of kidney transplant recipients, LN recipients had similar long-term graft survival and overall outcomes compared with non-lupus recipients when predictors are matched between groups.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Introduction Urinary tract infections (UTI) have been reported to occur with frequencies ranging from 30% to 60% in kidney transplant recipients during the first year posttransplantation. ...UTI is the main cause of infectious complications in this period. The objective of this study was to evaluate the incidence of UTI, during the first year posttransplantation and to identify the risk factors associated with its development, as well as its impact on graft function. Patients and Methods This retrospective cohort study had as a primary outcome the development of UTI, defined as the presence of more than 100,000 colony-forming units (CFU) of a pathogenic organism by mL of urine. The univariate analysis was performed with chi-square test for categorical variables and Student t test for continuous ones metrics. We performed multivariate analysis with logistic regression. P < .05 was considered statistically significant. Results We studied 176 kidney transplant recipients, including 54.5% of male gender and with an overall average age of 37 ± 12 years. The UTI incidence was of 35.8% (n = 63). The bacterium most frequently found in urine cultures was Escherichia coli (n = 46). In this study, the risk factors that were independently associated with UTI development were age, female gender, days of bladder catheterization, genitourinary anatomic alterations, and UTI during 1 month prior to kidney transplantation. Conclusion This type of study makes it possible to identify risk factors and to formulate strategies focused on particular risk factors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Human leukocyte antigen (HLA) antibodies were normally not found in subjects who have not been immunized by pregnancies, transfusions, or transplants. But with new methodology, we now see that HLA ...antibodies are often found in nonalloimmunized males.
The sera of 424 healthy male donors were tested with single antigen Luminex beads.
Human leukocyte antigen antibodies were detected in 63% of 424 male blood donors when a fluorescent value of more than 1000 was used as the cutoff. Antibodies to class I was found in 42%, class II in 11% and both in 12%. Five males who were tested eight times over a 6-month period consistently had the same specificity at similar strength levels at each testing. The antibodies reacted with specificities that are rare in the general population: 18.9% had antibodies to A*3002; more than 10% had antibodies to A*3101, B76, B*8201, and Cw*1701. About half of the donors with antibodies had one or two specificities; the other half had three or more specificities. Among those with class II specificities, 20.5% had antibodies to DPA1*0201/DPB1*0101, and 10.8% to DQA1*0503/DQB1*0301. Because the above data were obtained by testing sera of 424 Mexican donors, as a check, 29 males in Los Angeles were tested and shown to have similar specificities at roughly similar frequencies.
Normal males were found to have HLA antibodies to infrequent HLA specificities. It is likely that these HLA antibodies are produced to cross-reactive epitopes found in microorganisms, ingested proteins and allergens-making them natural antibodies.
We performed a retrospective cohort analysis to define the prognostic significance of vascular lesions documented in renal biopsies of lupus nephritis patients. A total of 429 patients were ...segregated into five groups: (1) no vascular lesions (NVL), (2) arterial sclerosis (AS), (3) non-inflammatory necrotizing vasculitis (NNV), (4) thrombotic microangiopathy (TMA), and (5) true renal vasculitis (TRV). Renal outcomes were analyzed by Cox regression models, and correlations between vascular lesions and activity/chronicity scores were determined by Spearman's coefficients. A total of 200 (46.6%) had NVL, 189 (44.0%) AS, six NNV (1.4%), 23 (5.4%) TMA, and 11 (2.6%) TRV. Patients with NVL were younger, with higher renal function; patients with TMA and TRV had lower renal function and higher arterial pressure at baseline. Antiphospholipid syndrome and positive lupus anticoagulant were more frequently observed in the TMA group. Five-year renal survival was 83% for NVL, 63% for AS, 67% for NNV, 31% for TMA, and 33% for TRV. NNV and TRV were significantly correlated with activity scores, while AS and chronic TMA were correlated with chronicity scores. Renal vascular lesions are associated with renal outcomes but do not behave as independent factors. The addition of vascular lesions to currently used scores should be further explored.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract This study defines 96 epitopes targeted by human leukocyte antigen (HLA) antibodies reported in the sera of normal healthy males with no history of deliberate alloimmunizations and in cord ...blood. These epitopes are accessible for antibody binding on either the intact or the dissociated forms of recombinant HLA class I single antigens. Sixty percent of the epitopes are accessible on dissociated antigens, are defined mostly by hidden amino acids, and are designated as cryptic epitopes. All 96 epitopes are located exclusively on A-, B-, or C-locus antigens except for one interlocus epitope. All sera in this study were tested in parallel, using single antigen beads that bear either intact or dissociated HLA antigens and antibodies with nearly identical specificities were identified in all tested sera. Because the specificities of these naturally occurring antibodies are unavoidably detected when testing for specificities of alloantibodies, it may be necessary to clearly differentiate the two forms of antibody. To date, the relevance of these antibodies in transplantation is unknown, but even if they are determined to be irrelevant to graft rejection, awareness of the newly identified epitopes could prove useful in avoiding the unnecessary exclusion of potential transplant donors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background:
Chronic kidney disease (CKD) is a global health problem. As it progresses to end stages, renal replacement therapy is required but ultimately, the best treatment is transplantation. ...Decreased renal function has been associated with an inflammatory state associated to primary CKD and in kidney transplant recipients (KTRs).
Objective:
To establish how the serum concentrations of some cytokines, such as interleukin (IL)-2, IL-8, IL-22, IL-17α, interferon-gamma, IL-4, and transforming growth factor-β, correlate with various CKD stages.
Methods:
One hundred and forty-one KTRs between the ages of 18 and 75 years were included in the study. We also included 112 live kidney donors, 37 CKD PGCKD+3, and 76 GPhealthy. Participants were grouped according to their glomerular filtration rate (GFR) and their circulating cytokine levels, previously quantified by ELISA.
Results:
By linear regression analysis, we established the relation of each cytokine with the GFR. Transforming growth factor-β correlated positively with the GFR in the study population, except in healthy individuals. A negative correlation of IL-8 and IL-17α and GFR was found in all cases.
Conclusions:
Whether these cytokines (IL-8 and IL-17α) could be used as inflammatory biomarkers indicating CKD progression, regardless of the type of population, remains to be prospectively determined.
Angiotensin II type 1 receptor agonist antibodies (AT1R-AAs) have been associated with hypertension, atherosclerosis and vascular inflammation in human diseases. The aim of the study was to evaluate ...the prevalence of AT1R-AAs in active lupus nephritis (LN) patients and their association with vascular damage. One hundred and seven active LN patients underwent a complete clinical examination, measurement of AT1R-AAs, ambulatory blood pressure monitoring, carotid intima-media thickness measurement and morphometric analysis of subintimal fibrosis and medial hyperplasia of the vessels in the kidney tissue. Plasma AT1R-AAs were positive in 58 (54.2%) patients. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, complement C3 and C4 levels and titers of anti-dsDNA antibodies were higher in the group with positive AT1R-AAs compared with those with negative AT1R-AAs. The AT1R-AA titers correlated with anti-dsDNA antibody titers and with complement C3 and C4 serum levels. In the kidney biopsy, the percentage of subintimal fibrosis and the area of medial hyperplasia were greater in the AT1R-AA-positive patients. No differences in arterial pressure, carotid intima-media thickness and response to therapy were detected. In conclusion, AT1R-AAs are prevalent in active LN patients and are associated with histologic features of microvascular damage.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We performed a retrospective cohort analysis focusing on lupus nephritis renal flare incidence and outcome predictors. One hundred and eighteen patients with biopsy-proven lupus nephritis were ...segregated by induction/maintenance regimes. The primary outcome was the proportion of patients experiencing renal flare. Secondary assessment included doubling of serum creatinine and development of end-stage renal disease. After a median follow-up of 31 months (interquartile range 21–46) from the date of response to induction therapy, 47 patients (39.8%) developed a renal flare. Azathioprine-maintained patients had a higher risk of renal flare compared with mycophenolate mofetil-maintained patients (hazard ratio 2.53, 95% confidence interval 1.39–4.59, p < 0.01). Age (hazard ratio 0.96, 0.92–0.99, p = 0.03), serum creatinine at presentation (hazard ratio 1.76, 1.13–2.76, p = 0.01), complete remission after induction therapy (hazard ratio 0.28, 0.14–0.56, p < 0.001) and azathioprine maintenance therapy (hazard ratio 4.78, 2.16–10.6, p < 0.001) were associated with renal flare on multivariate analysis. Ten patients progressed to end-stage renal disease (8.5%) by a median 32.5 months. Age (hazard ratio 0.88, 0.77–0.99, p = 0.05), complete remission after induction therapy (hazard ratio 0.08, 0.01–0.94, p = 0.04) and severe nephritic flare (hazard ratio 13.6, 1.72–107.7, p = 0.01) were associated with end-stage renal disease development. Azathioprine maintenance therapy is associated with a higher incidence of relapse in the Mexican-mestizo population. Younger age and nephritic flares predict development of end-stage renal disease.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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