Role of anti-CCP in diagnosis of rheumatoid arthritis in comparison to rheumatoid factor

Background: RA is a chronic inflammatory disease that primarily affects the diarthroidal joints. Persistence and progression of the disease is regulated by immune mediators that continue to be defined and provide targets for immune intervention. Anti-CCP Antibodies were detected in over 80% of RA sera. This serological test has advantage of easy performance by convenient enzyme linked immunosorbent assay test

Aim of Work: This study was conducted to assess the value of anti-CCP as a marker for diagnosis and disease activity in RA patients

Subjects and Methods: The study was conducted on 75 subjects [25 RA patients, 25 disease control patients and 25 normal healthy individuals that served as a control group]. Serum anti-CCP level was measured using ELISA test. While Serum RF was measured using immune nephelometry

Results: Serum anti-CCP level was significantly higher in RA patients compared to the disease control group and the control group. Its level showed a positive significant correlation with RF, CRP, and the disease activity score. Sensitivity of the test was 74%, specificity was 100%, positive predictive value was 100% and negative predictive value was 73.5%

Conclusions: Detection of serum anti-CCP antibody in RA patients is a laboratory test that can be used as a parameter to diagnose RA

Apoptosis of peripheral blood cytotoxic T lymphocytes in chronic hepatitis C virus infection: relation to disease severity and response to therapy

More than 80% of HCV-infected individuals develop chronic disease, which can progress to liver cirrhosis and hepatocellular carcinoma. T cell-mediated protection against HCV depends on constantly activated effector CD8+ T cells that control emergence, spread and expansion of the virus. Why these cells fail to contain HCV replication in 70-80% of the individuals who develop persistent viremia is not clear. Fas receptors [APO-1 or CD95] and the Fas ligand system [Fas/FasL] have been implicated in the induction of apoptosis which is related with the pathogenesis of hepatitis C. Was to assess the expression of CD95 [Fas/APO-1] [as an apoptotic marker] on peripheral blood cytotoxic T lymphocytes from patients with chronic HCV infection and to correlate this with disease severity in the liver, response to antiviral therapy and extrahepatic autoimmune manifestations. Thirty patients with evidence of chronic HCV infection and 10 healthy age and sex matched volunteers with negative HCV antibodies sera serving as controls were enrolled into the present study. Our patients were classified into two main groups according to antiviral therapy, Group A: They were 17 patients not receiving treatment and Group B: They were 13 patients who received antiviral therapy for 24 weeks. Group A patients were further subdivided according to the presence or absence of extrahepatic manifestations into two groups: Group I: They were 11 patients not receiving therapy and had no extrahepatic manifestations. Group II: They were 6 patients not receiving therapy and had extrahepatic manifestations. Group I patients were also subdivided according to the necroinflammatory score in liver biopsy into three groups with: Mild, moderate and severe disease activity. They were also subdivided as regard fibrosis stage in liver biopsy into groups with: Moderate and severe fibrosis. Group B patients were further subdivided according to their response to antiviral therapy into: Group III: 6 patients received therapy and were non responders and Group IV: 7 patients received therapy and showed good response. After detailed history taking and thorough clinical examination, the following investigations were done: CBC, AST and ALT, serum cryoglobulins [for patients with extrahepatic disease] and flowcytometric estimation of the percentage of apoptotic peripheral blood cytotoxic T lymphocytes [CD8+CD95+] and non apoptotic cytotoxic T lymphocytes [CD8+ CD95-]. Current liver biopsy was performed in patients of Group I and examined histopathologically. There was highly statistically significant difference between HCV patients and controls as regard ALT, percentage of apoptotic cytotoxic T lymphocytes [CD8+ CD95+] and non apoptotic cytotoxic T lymphocytes [CD8+ CD95-] [p<0.001]. There was statistically significant difference between patients of Group I, II, III, IV and controls in percentage of CD8+CD95+ and CD8+CD95- cells. Comparison between Group I and II revealed non significant difference in percentage of CD8+CD95+ and CD8+CD95- cells or in percentage of CD8-CD95+ cells [apoptotic non cytotoxic T] [p>0.05]. Comparison between Group III and IV revealed statistically significant difference in percentage of CD8+CD95+ and CD8+CD95- cells [p<0.05]. In Group I the percentage of CD8+CD95+ tended to correlate with activity index of liver biopsy but significantly correlated with serum ALT in Group III. In Group II significant positive correlation between percentage of CD8+CD95+ and AST with tendency toward correlation with ALT was found. Also percentage of CD8+CD95+ correlated with purpura and arthritis but not with cryoglobulinemia. Percentage of CD8+CD95+ showed non statistically significant correlation except with serum prothrombin time in group IV. There was increase in the percentage of CD8+CD95+ cells in higher grade of necroin-flamatory activity and in higher stage of fibrosis in liver biopsy in group I. Our findings support the suggestion of major role of peripheral blood CD8+ T cells in elimination of HCV and suggest that cellular immune response plays a key role not only in viral elimination, but also in liver pathology associated with HCV-infection. Monitoring apoptosis of CD8+ T cells by measuring FAS expression is useful in follow-up of antiviral response in these patients. Finally, Fas/FasL pathway is critical in persistent HCV infection in humans and represents a potential target for restoring function of exhausted HCV-specific CTLs

Fas expression on peripheral blood t lymphocytes in systemic lupus erythematosus [SLE]: relation to disease activity and lupus nephritis

Introduction: Systemic lupus erythematosus [SLE] is an autoantigen driven T cell dependent autoimmune disease. Lupus nephritis is one of the most serious complications in SLE, occurring in up to 60% of the patients. SLE patients show increased apoptosis of peripheral blood mononuclear cells [PBMCs], especially T lymphocytes and decreased resistance of activated T cells to apoptosis. Fas, also known as APO-1 or CD95, is a cell surface protein that triggers apoptotic cell death with characteristic cytoplasmic and nuclear condensation and DNA fragmentation. The aim of this work was to evaluate Fas expression [as an apoptotic marker] on peripheral blood T lymphocytes in SLE patients in relation to disease activity and lupus nephritis

Subjects and methods: Thirty-five SLE patients and 15 normal controls were studied. Disease activity was assessed by SLAM score and patients were divided according to: a] disease activity [mildly active group with SLAM score <6, moderately active group from 6-12 and severely active group >12], b] the clinical presentation including the presence or absence of either lung, cardiac, neurological affection or nephritis as well as regard, c] WHO classes of lupus nephritis. Laboratory investigations included CBC, ESR, serum creatinine, urine examination, 24 hours urinary proteins, ANA and Anti-dsDNA, flowcytometric analysis of percentage of Fas expression [CD95+] on peripheral blood T lymphocytes [CD3+] and percutaneous renal biopsy in indicated patients with evidence of nephritis

Results: Percentage of CD3+CD95+ cells from SLE patients was statistically significantly increased compared to healthy controls [p<0.05]. Comparative study among the patients according to SLAM score was statistically significant [p<0.05] using ANOVA test with the highest percentage of apoptotic T lymphocytes in severely active group. When comparing each group with the control one, results showed statistically significant more apoptotic T cells in severely active SLE patients compared with controls. However, although the apoptotic T cells were increased in moderately active SLE patients, the data did not reach statistical significance in comparison with healthy controls nor with the mildly active group [p > 0.05]. Apart from nephritis [p<0.05], Fas expression was not associated with the clinical presentation of the patients, as regard the presence or absence of lung, cardiac or neurological affection [p>0.05]. The percentage of Fas expression was higher in class IIb than either class III or IV as well as patients without nephritis and those with nephritis without indication for renal biopsy [27.32+/-13.62 vs. 19.8, 19.14+/-5.12, 14.8+/-3.57 and 17.2+/-6.8]. However, on comparing only the patients who did renal biopsy, the renal parameters as well as the percentage of CD3+CD95+ cells was statistically non significant [P > 0.05]. Correlation between the percentage of CD3+CD95+ cells and different parameters revealed highly significant positive correlation as regard ESR, current steroid treatment dose and SLAM scoring, [p<0.001], statistically significant positive correlation as regard platelets, nephritis, arthritis, fever, lymphadenopathy and chronicity index in renal biopsy [p < 0.05], and tendency toward urinary albuminuria and casts. [p= 0.061 and 0.056 respectively]

In conclusion: The increased CD3+ CD95+ cells from patients with SLE and its correlation with disease activity suggests that abnormalities of apoptosis may be related to the pathogenesis of the disease [especially with high grades of activity] and its serious complication, nephritis. In patients with nephritis, the lower Fas expression [CD95+] on peripheral blood T lymphocytes [CD3+] in patients with class IV nephritis than those with class IIb nephritis could be possibly explained by the effect of treatment or by the natural process of the proliferative disease itself. However, further studies including large number of SLE patients, evaluating apoptosis both systemically and locally in tissue biopsies and studying various apoptotic pathways are needed to understand its role in the pathogenesis of the disease and its value as a therapeutic target

Retrospective study of infections in Egyptian patients with systemic lupus erythematosus [SLE]

Infections are one of the leading causes of morbidity and mortality in patients with systemic lupus erythematosus [SLE], therapeutic, dose-related and genetic factors all contribute to a lupus patient's increased susceptibility to infections. Although bacterial pathogens are the most common cause of infections, a wide variety of pathogens have been reported. Multiple risk factors for infection in SLE have been reported. These include disease activity, renal disease, gluco-corticoid use and cytotoxic therapies. The objective was to analyze infection risk factors in Egyptian lupus patients; the influence of these factors on disease activity, organ damage, disease development and the type of micro-organisms involved. The study included forty patients with SLE [37 females and 3 males] They were selected from those attending the SLE clinic in Ain Shams University hospital outpatient. Lupus disease activity had been established according to SLAM score. They were subjected to a retrospective study to : Complete medical history with special interest on duration of the disease, current treatment for lupus and dosage of prednisone, antimalarial drugs and immunosuppressive agents, number of infections whatever the cause during One year and number of admission due to episodes of infection whatever the cause. It included also symptoms of urinary tract infection [UTI] upper respiratory tract infection [URTT] as well as any complaint of the patient proved to be due to infection Laboratory assays included: CBC, ESR, serum creatinine, urine analysis, 24 hours protein in urine and culture when necessary. Increased incidence of infection in lupus patients which was 83 infections during the one year study. the incidence of Upper Respiratory Tract Infections was 8 infections [9.64%], Urinary Tract Infections 70 infections [84.34%], and Skin Infections 5 infections [6.02%] 83% of the cultures had had obtained from lupus patients. 83% of the urine were G- ve organisms. E. coli was the most common uropathogen encountered in this study [47%] which was resistant to most antibiotics but was sensitive to aminoglycosides. Skin infections were presented by abscesses 4 times [80%] -with predominance of staphylococci- and Herpes Zoster once [20%] There was a significant increase in the number of infection in relation to corticosteroids dose. There was a statistical significance between incidence of infection and addition of immunosupressive drugs to corticosteroids. There was a strong relation between incidence of infection and disease activity. SLE itself, increased dose of corticosteroids, use of immunosuppressive drugs and activity of the disease all are risk factors in incidence of infection in patients with SLE. UTI followed by URTI and skin infections including HZ were the most frequent infections in Egyptian SLE patients

Diagnostic role of anti-RA33 autoantibody in early rheumatoid arthritis. does MRI improve the diagnostic sensitivity?

Introduction: There are inherent difficulties in making an accurate diagnosis or RA in early stages. The Aim of This Study was to determine the value or the anti -RA33 antibodies alone or in combination with MRI for the diagnosis or early RA and for the differential diagnosis of unclassified arthritis. Also, a comparison of ultrasonography, magnetic resonance imaging and plain radiography in their sensitivities for detection of early joint pathology in early RA was revised

Patients: This study included 67 patients. The patients were further classified into 3 main groups. Group I [18 patients]: patients with unclassified arthritis of less than 6 months duration. This group was followed up for 24 months. Group II [12 patients]: patients with established rheumatoid arthritis. Group III [37 patients]: patients with non - RA peripheral poly- or oligo-arthritis

Methods: For all the patients full clinical examination as well as routine laboratory investigations were performed in addition to anti-RA33 antibodies. Plain radiographs of affected joints were taken and repeated at least once during follow-up as well as anti- RA33 antibodies for the patients of unclassified group who developed RA. For the unclassified group, in addition, joint US and MRI were done

Results: Group I [n = 18]: In patients with unclassified arthritis, eight [44.44%] patients were negative for anti - RA33 and 10 patients were positive. Sixteen patients were negative for RF and 2 patients were positive for RF. After follow up period, 8 patients were negative for anti - RA33 and 10 patients were positive. However, 12 patients were negative for RF and 6 patients were positive. After follow up, 10 patients developed RA. From the 10 patients who developed RA, 8 patients were anti - RA33 positive and 2 patients were positive for RF at start of the study. At the end of the study, the percentage of the positive patients, for the anti - RA33 remained the same [80%]. However, the percentage of patients having positive RF increased up to 60%. The sensitivity of anti -RA33 in detecting early RA in this group was 80%, while that of RF was 20%. As regard radiological findings in our study, US was highly sensitive in diagnosis and quantification of synovitis in all patients with RA in early stage. However, it was less sensitive than MRI in detection of erosions and tenosynovitis. MRI sensitivity and specificity in detection of early RA was 70% and 75%. Combination of MRI with anti - RA33 in detection of early RA increased the sensitivity of both of them into 100%. In the unclassified group, the patients who developed later on RA had significantly less disease duration, significantly higher clinical probability of the disease with higher RAI, higher total leucocytic count, higher ESR as well as significantly higher anti - RA33 antibody level at the start of the study. Also, these patients had higher prevalence of erosions in MRI. In Group II [n = 12]: Patients with established rheumatoid arthritis: 4 patients were negative for anti - RA33 antibodies and 8 patients were positive. Also, 4 patients were negative for RF and 8 patients were positive. At the end of this study, we had 22 patients with RA, 12 were positive for the anti - RA33 antibodies and 10 were negative. Fourteen of them were positive for RF and 8 patients were negative for RA. Group UI [n = 37] patients with non - RA peripheral poly- or oligo-arthritis, when excluding the patients with SLE, the anti n RA33 was found to be negative in all patients with other forms of arthritis. ln the meantime, RF was found to be positive in 6 patients. ln SLE patients [n = 9] the anti - RA33 was found to be positive in 6 patients and RF was positive in 4 cases. The anti - RA33 showed highly significant correlation with the presence of active nephritis and significant correlation with erosive arthropathy. At the end of this study, the sensitivity and the specificity diagnosis of RA by using anti - RA33 antibody was 72.73%, and 83.78% respectively and that of MRI in detection of early RA was 70% [7/10] and 75% [6/8]. The sensitivity raised up to 100%, when using both tools in the diagnosis

Conclusion: Anti-RA33 autoantibody is a marker for early RA. It can differentiate RA from other non-RA rheumatological arthritis. Also, it can define a subset of SLE patients with erosive arthritis and active nephritis. MRI is a sensitive method in detecting erosion in early RA. Anti-RA33 antibody assay together with MRI can be very useful as adjunctive criteria to the ACR classification criteria for diagnosis of early RA