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"nBackground: There are several evidences that genetic factors besides environmental triggers have important role in initiating the rheumatoid arthritis (RA). The aim of this study was to investigate the association of rheumatoid arthritis with different subtypes of HLA DR4 in Iranian patients. "nMethods: In an un-matched case control study, 110 rheumatoid arthritis patients (case) and 56 knee osteoarthritis patients (control) of outpatient clinic in Shariati Hospital were entered to the study. After blood sampling from case and control groups, DNA was isolated by using salting-out method and HLA DR4 and its subtypes were detected. Association of HLA DR4 and its subtypes with rheumatoid arthritis, rheumatic factor and clinical manifestations of diseases was evaluated. "nResults: Eighty nine (80.9%) of rheumatoid arthritis patients were female and 21 were male. Thirty four of the RA patients (30.9%) and eleven subjects from the control group (19.6%) were HLA DR4 positive (p=0.12). The most frequent subtype of HLA DR4 in RA patients was 0404 and in control group was 0401 (p=0.03). There were not statistically significant association between HLA DR4 and age of disease onset, family history, morning stiffness and rheumatoid factor. Joint swelling and tenderness had association with HLA DR4 (p=0.04 and p=0.03). "nConclusion: Although there were no statistically significant association between rheumatoid arthritis and HLA DR4, but prevalence of this HLA was higher in patients than control. It is possible that in some ethnics, other HLAs may have role in pathogenesis of disease.

Childhood diabetes is thought to usually result from autoimmune beta cell destruction (type 1A) with eventual total loss of beta cells. Analysis of C-peptide in children characterised at diabetes onset for autoantibodies shows heterogeneous preservation of insulin secretion in long-standing diabetes. The aim of this study was to characterise the pancreases of childhood-onset diabetes in order to define the pathological basis of this heterogeneity. We evaluated 20 cadaveric organ donor pancreases of childhood-onset long-term patients for disease heterogeneity and obtained corresponding C-peptide measurements. Pancreases from the majority of cadaveric donors contained only insulin-deficient islets (14 of 20). The remaining six patients (30%) had numerous insulin-positive cells within at least some islets, with two different histological patterns. Pattern A (which we would associate with type 1A diabetes) had lobular retention of areas with ‘abnormal’ beta cells producing the apoptosis inhibitor survivin and HLA class I. In pattern B, 100% of all islets contained normal-appearing but quantitatively reduced beta cells without survivin or HLA class I. Our data demonstrate that C-peptide secretion in long-standing diabetic patients can be explained by two different patterns of beta cell survival, possibly reflecting different subsets of type 1 diabetes. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic and debilitating disease affecting approximately 2.5 million people worldwide, and safe and effective treatment options are sorely lacking. While there are several currently approved drugs that have shown some efficacy at reducing the relapse rate in patients with the relapsing-remitting form of the disease, the impact of this outcome relative to long-term disease progression is unknown. Effective treatment for those with primary or secondary progressive MS is practically nonexistent. Dirucotide (MBP8298) is a synthetic peptide that has shown promise at increasing time to progression with little or no associated toxicity in Phase II studies. The drug is specifically designed to induce tolerance in patients with HLA types DR2 and/or DR4, although patients with other HLA subtypes may also benefit. Dirucotide is now being evaluated in two large Phase III secondary progressive MS trials, as well as a smaller Phase II relapsing-remitting MS trial. [ABSTRACT FROM AUTHOR]

The Class II human leukocyte antigen (HLA) DRB1 antigen DR4 is associated with autoimmune disorders and response to cyclosporine immunosuppression in T-lymphoproliferative disorders. We retrospectively reviewed the role of HLA DR4 on outcomes in 77 related and 22 unrelated consecutive first HLA-matched alloHSCT patients with lymphoid malignancies treated between 1992 and 2003. HLA DRB1 typing was determined by molecular (n = 69) or serologic (n = 30) methods. The proportion of patients with one HLA DR4 antigen was 18% (18/99). At a median follow-up of 5.6 years, there were no significant differences in aGvHD, cGvHD and OS between the HLA DR4 positive versus negative patients in any disease or donor subgroups. Nine of 18 (50%) DR4 positive patients and 20 of 81 (25%) DR4 negative patients had disease progression post HSCT (p = 0.033). Progression-free survival (PFS) at 3 years was 29% in the DR4 positive group and 70% in the DR4 negative group (p = 0.004). In univariate and multivariate analyses, DR4 positivity was the only significant factor associated with PFS (RR = 3.2, p = 0.007). Our results suggest that in addition to the known role of HLA DRB1 disparity in mediating histocompatibility, HLA DR4 is associated with inferior PFS in patients with lymphoid malignancy undergoing alloHSCT. [ABSTRACT FROM AUTHOR]