HLA-DRB1 alleles in Egyptian children with systemic lupus erythematosus

Systemic lupus erythematosus [SLE] is an autoimmune disease characterized by multisystem organ damage due to autoantibody production. Polymorphism in genes at the Major histocompatibility complex [MHC] region represents an important susceptibility factor for SLE, especially HLA-DRBI and HLA-DQB1. Moreover; it was noted that ethnicity has a significant role in both disease susceptibility and disease expression. This work was planned out to study HLA-DRBI alleles association with SLE susceptibility and clinical presentations in Egyptian children with juvenile onset SLE. HLA-DRBI allele typing was done using polymerase chain reaction-sequence-specific oligonucleotide probe for 65 juvenile SLE patients and compared to 150 healthy controls of the same ethnic group. P values were corrected for the number of the alleles tested [Pc]. HLADRB1 asterisk 15 allele was significantly increased in SLE children Vs controls [OR=3.44; 95%CI=1.51-7,83; P=0.004 and Pc=0.048]. No HLA-DRB1 allele was found to be statistically significantly associated with renal, musculoskeletal, cutaneous, hematologic, cardiac or neuropsychiatric manifestations in children with SLE [P>0.05]. Although HLADRB1 asterisk 15 [15g] allele may be a susceptibility allele in Egyptian children with juvenile SLE; however HLA-DRB1 alleles do not contribute to SLE clinical presentations in these children

Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis and their clinical significance

One of the characteristics of rheumatoid arthritis [RA] is the presence of several autoantibodies in the serum of the patient. However, most of these antibodies have failed to demonstrate adequate diagnostic and prognostic value so far. There is growing evidence that therapeutic intervention early in the course of RA leads to earlier disease control less joint damage, and a better prognosis. A new serological test, the anti-cyclic citrollinated peptide [anti-CCP] was developed. Anti-CCP was reported to have a high specificity for the diagnosis of RA, especially in patients with early disease and its presence before disease presentation is suggestive of its role in disease pathogenesis .The aim of this study is to estimate the level of anti-CCP antibodies in the serum of RA patients and to correlate them with RF isotypes [IgG and IgM] and clinical findings as disease activity and severity. This study comprised 68 RA patients [64 female and 4 males] diagnosed according to the revised criteria described by ACR [1987], in addition to 15 healthy control subjects. Clinical assessment of RA disease activity and severity, radiological investigations, and laboratory investigations [complete blood picture, ESR, CRP, determination of anti-CCP, IgG-RF and IgM-RF antibodies by ELISA technique] were done for all subjects.Highly significant increase in the levels of anti-CCP, IgG-RF and IgM-RF antibodies were found in RA patients compared to control group [P<0.001 for each]. Anti-CCP antibodies showed the highest diagnostic specificity [100%] than both RF IgM and IgG [93.33% for each].The anti-CCP and IgG-RF tests had excellent sensitivity [95.59% and 98.53% respectively] while IgM-RF had relatively lower sensitivity than both tests [86.76%]. Anti-CCP level was significant positively correlated with duration of the disease [P=0.024].Also,there was positive correlation between anti-CCP levels and all disease activity parameters which include the number of active joints [P=0.007], duration of morning stiffness [P<0.001], ESR [P<0.001] and CRP values [P=0.024]. Anti-CCP test had the best correlation with disease activity grades .disease severity, and radiological score [P=<0.001, P=<0.001 and P=0.000 respectively]. The level of anti-CCP in patients receiving methotrexate either alone or with lefwnomide is lower than other patients receiving methotrexate with corticosteroids [56.5 +/- 41.33,112 +/- 95.04 lU/ml respectively]. In conclusion, anti-CCP antibodies could be regarded as a new diagnostic marker for RA as they have 100% specificity and 95.8% sensitivity and it could predict erosive development early in the disease, and it could be used in evaluation of disease activity, severity and therapeutic response

Proinflammatory cytokines [IL-12 and IL-18] in immune rheumatic diseases: relation with disease activity and autoantibodies production

lnterleukin-18 [IL-18] and its inducer IL-12 have multiple biological activities that are important in generating Th1 responses and inflammatory tissue damage. We investigated serum concentration of the novel pro-inflammatory Th1 cytokine; IL-18, and its inducer IL-12 in patients with immune rheumatic diseases. Group I comprised 32 patients of systemic lupus erythmatosus [SLE], Group II comprised 36 patients of rheumatoid arthritis [RA]. Group III comprised 9 patients [2 patients of Behcet, 2 patients of Dermatomyositis, 2 patients of Sicca syndrome, one patient of Scleroderma, and 2 patients of Mixed connective tissue disease]. Group IV is a control group consists of 21 sex and age matched healthy subjects and correlated their levels with autoantibody concentration [ANA and ds-DNA], clinical grades and SLE disease activity index [SLEDAI]. Serum IL-18, IL-12 ,ANA and ds-DNA were measured by enzyme immune sorbent assay. IL-18, IL-12 and ANA were significantly higher in the three studied groups than in the control group [IL-18; P<0.001 in the three groups, IL-12; P=0.019, P=0.002, and P= 0.006, and ANA; PO.001, P=0.002,and P=0.006, respectively].ds-DNA was significantly higher in SLE patients than in control group [P<0.001].There were significant positive correlations between; A] levels of IL-18,and both ANA and ds-DNA in SLE patient [r=0.41,P=0.001, r= 0.58 and P=0.001 respectively]; and B] IL-18 and ANA in both RA and group III patients [r= 0.32, P=0.005,r=0.61 and P= 0.022 respectively]. Also, there were significant positive correlation between the levels of IL-18 and clinical grades of the three groups [r=0.60, P=0.001, r=0.79, P=0.001, r=0.78 and P= 0.001 respectively]. In SLE patients ,IL-18 concentration shows significant positive correlation with SLEDAI score [r= 0.76 ,P=0.001]. In conclusion, the elevation of proinflammatory cytokines [IL-18 and IL-12] may trigger the inflammatory process in immune rheumatic diseases and IL-18 is correlated with disease activity