Characteristics of rheumatoid arthritis patients with concomitant hepatitis C virus infection

Introduction

Hepatitis C virus (HCV) is frequently associated with rheumatic autoimmune manifestations including rheumatoid-like arthritis.

Aim of the work

This work is aimed to study the impact of concomitant HCV infection on rheumatoid arthritis (RA) patients.

Patients and methods

110 RA patients (mean age 44.6 ± 12.7, disease duration 7.92 ± 6.56 years) were included. HCV infection was diagnosed by HCV-antibody (HCV-Ab) and polymerase chain reaction. Disease activity was assessed using the disease activity score 28 (DAS28) and radiological damage by a modified Larsen method. Functional disability was assessed by the Modified Health Assessment Questionnaire (MHAQ).

Results

HCV-Ab was detected in 20% and viremia in 12.7% of RA patients. HCV-Ab positive patients were significantly older (p < 0.001) and had a longer disease duration (p = 0.02). No differences were found between HCV-Ab positive and -negative patients in DAS28 and modified Larsen’s scores, however, HCV-Ab positive patients had a higher frequency of deformities (p < 0.005) associated with older age (p < 0.001) and higher MHAQ scores (p = 0.002), independent of age and disease duration. They also had a higher frequency of hepatomegaly (p < 0.001) and vasculitis (p < 0.001). Hepatomegaly was associated with older age (p = 0.004) and longer disease duration (p = 0.003) while vasculitis was associated with older age (p = 0.02).

Conclusion

Concomitant HCV infection in RA patients is associated with significant disability and comorbidities in the form of hepatomegaly and vasculitis. Hepatomegaly and vasculitis were associated with older age. Hepatomegaly was also associated with longer disease duration. Screening for HCV infection is recommended in Egyptian RA patients.     

The association of anti-CCP antibodies with disease activity in rheumatoid arthritis

Antibodies to citrullinated proteins have been described in patients with rheumatoid arthritis (RA) and these appear to be the most specific markers of the disease. Our objective was to determine the frequency of antibodies to cyclic citrullinated peptides (CCPs) in patients with RA and the association of anti-CCP antibodies with disease activity, radiological erosions and HLA DR genotype. Forty patients with RA and 38 patients with fibromyalgia were included in this study. Serum samples were collected from both patient groups with RA and fibromyalgia. Anti-CCP was measured by the corresponding enzyme-linked immunosorbent assay. Additionally, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), disease activity score (DAS), visual analog scala (VAS), HLA genotype and radiographic information were determined in patients with RA. The rate of sensitivity and specificity of anti-CCP reactivity for the diagnosis RA were measured (sensitivity 50%, specificity 100%). There is no significant difference between anti-CCP (+) and anti-CCP (-) RA patients for DAS28, VAS, ESR, CRP, disease duration, HLA genotype, and radiological assessment of hand. However, there was a significant difference between anti-CCP (+) and anti-CCP (-) RA patients for RF and the radiological assessment of left and right wrists (respectively, P < 0.05, P = 0.04, P = 0.01). There was no significant correlation between anti-CCP antibody and ESR, CRP, VAS, DAS 28 or radiological assessment. A small but significant correlation was found between RF and anti-CCP antibody (P = 0.02, r = 0.35).     

Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.     

High positivity of anti-CCP antibodies in patients with Down syndrome

The aim of the present study was to evaluate the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in patients with Down’s syndrome (DS) previously tested for IgM rheumatoid factor (RF) and to correlate the results with clinical findings. Eighty-eight patients with DS previously tested for IgM-RF were divided into two groups matched for sex and age. Group A consists of 42 RF positive patients and group B of 44 RF negative patients. The presence of anti-CCP antibody was determined using a second-generation enzyme-linked immunosorbent assay. A total of 52.3% (45/86) of DS patients were positive for anti-CCP antibodies. Twenty-four patients (57.1%) of the RF positive group and 21 (47.7%) of the RF negative group presented anti-CCP circulating antibodies. The concordance between both tests was 54.6%. None of the patients had clinical evidence of rheumatoid arthritis or juvenile idiopathic arthritis. Although a high prevalence of anti-CCP antibodies was observed in DS patients, no association has been found presently with clinical disease. Careful follow-up of these patients will be necessary to clarify the real significance of these findings.     

Anti-CCP hs (high sensitive) in Egyptian rheumatoid arthritis patients associated with chronic hepatitis C virus infection

Aim of the workThe objectives of this study were to evaluate the use of anti-cyclic citrullinated peptide high sensitive (anti-CCP hs) in the differentiation between rheumatoid arthritis (RA) and chronic hepatitis C virus (HCV) associated arthropathy and its correlation with disease activity and the degree of liver cirrhosis in RA associated with chronic HCV infection.Patients and methodThis study was carried out on 90 chronic HCV infection patients, 90 HCV negative RA patients and 90 HCV positive RA patients, in addition to 90 healthy volunteers. Hepatic assessment, rheumatological examination, quantitative HCV RNA test and abdominal ultrasonography were assessed in all HCV patients. Disease activity score (DAS-28) was assessed in RA patients. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibodies (ANA), cryoglobulins, rheumatoid factor (RF), anti-CCP3, anti-CCP hs test were assessed for all patients.ResultsThe higher frequency of anti-CCP hs was found in RA (HCV+ve) (88.9%) compared to RA (HCV-ve) (75.5%) and HCV patients (14.4%), its sensitivity in RA patients was 75.6% and specificity was 85.6%. In HCV patients anti-CCP hs significantly correlated with cryoglobulinemia and scoring for liver fibrosis (p < 0.001). In RA patients, anti-CCP hs significantly correlated with RF, anti-CCP3, DAS-28, ESR and CRP (p < 0.001).ConclusionsSerum anti-CCP hs is sensitive but not a specific marker for RA patients and cannot be used as a diagnostic marker to differentiate between RA and chronic HCV associated arthropathy, in addition it cannot be used as a marker of activity in RA especially when associated with HCV.     

抗Sa抗体、抗环瓜氨酸肽抗体、葡萄糖6-磷酸异构酶抗原和类风湿因子联合检测对类风湿关节炎的诊断意义

目的 探讨抗Sa抗体、抗环瓜氨酸肽(CCP)抗体、葡萄糖6-磷酸异构酶(GPI)抗原及类风湿因子(RF)联合检测对类风湿关节炎(RA)诊断的意义.方法 采用酶联免疫吸附试验(ELISA)检测抗Sa抗体、抗CCP抗体及RF亚型RF-IgA、RF-IgG、RF-IgM,免疫比浊法检测RF.结果 抗Sa抗体、抗CCP抗体、GPI抗原、RF对RA诊断的特异性和敏感性分别为95.69％和59.79％、98.28％和90.72％、76.14％和78.35％、67.24％和91.75％.RF-IgA、RF-IgG、RF-IgM对于RA诊断的特异性和敏感性分别为89.66％和58.76％、90.52％和68.04％、79.31％和79.38％.两项指标联合检测对RA诊断的特异性和敏感性为92.24％ ～ 100.00％和47.42％～86.60％;3项指标联合检测对RA诊断的特异性和敏感性为99.14％～100％和46.39％～71.13％;4项指标联合检测对RA诊断的特异性和敏感性为100.00％和46.39％.抗Sa抗体阳性组患者C反应蛋白水平高于阴性组(P＜0.05).结论 两项及两项以上指标联合检测可以显著提高RA诊断的特异性,有利于RA的早期诊断及治疗.     

Predictive value of antibodies to cyclic citrullinated peptide in patients with early arthritis

The objective of this study was to determine the diagnostic value for rheumatoid arthritis (RA) of antibodies to cyclic citrullinated peptides (anti-CCP) in patients with early arthritis and vasculitis. Sixty-four adult patients with early arthritis and disease duration of less than 4 months were clinically diagnosed by an experienced rheumatologist as having RA (n=27), spondyloarthropathy (n=11), and undifferentiated arthritis (n=26). Eighteen patients with vasculitis were also included in the study. The patients with early arthritis were followed up for 9 months. After the follow-up period, five of 26 patients with undifferentiated arthritis were diagnosed as having RA. All serum samples were tested for anti-CCP and IgM rheumatoid factor (IgM-RF). The anti-CCP positivity in RA patients (44.4%) was significantly more frequent than in patients with undifferentiated arthritis (3.8%), spondyloarthropathy (0%), and vasculitis (5.6%) (p=0.001, p<0.01, and p<0.01, respectively). The frequency of IgM-RF positivity was 40.7% in RA, 7.7% in undifferentiated arthritis, 0% in spondyloarthropathy, and 22.2% in vasculitis groups. The respective specificity of anti-CCP and IgM-RF tests for early RA were 97.3 and 94.6%, and the respective sensitivity of them were 44.4 and 40.7%, respectively. The combination of anti-CCP and IgM-RF positivity had a very high specificity and positive predictive value (100%) but a rather low sensitivity (33.3%). When either anti-CCP or IgM-RF positivity combined into one criterion, the sensitivity became high (51.9%) but the specificity decreased to 91.9%. Overall performance of anti-CCP test alone for the early RA was higher than IgM-RF and the combination of anti-CCP and IgM-RF (p<0.05), and was similar to the combination of anti-CCP or IgM-RF. The specificity of positive anti-CCP test for diagnosis of established RA reached up to 100%. In conclusion, the anti-CCP test is a new diagnostic test with extremely high specificity for RA. Anti-CCP antibody testing combined with IgM-RF testing has additional value over IgM-RF testing alone in patients with early arthritis.     

Anti–tumor necrosis factor agents for rheumatoid arthritis in the setting of chronic hepatitis C infection

Objective

To examine the safety of using anti–tumor necrosis factor (TNF) therapy in patients with rheumatoid arthritis (RA) in the setting of hepatitis C virus (HCV) infection.

Methods

The charts of 5 patients known to have RA requiring anti‐TNF therapy as well as established HCV infection were reviewed retrospectively for laboratory data of hepatic parenchymal inflammation and viral proliferation while taking these agents.

Results

In a mean ± SD followup period of 41 months (± 28.2 months), no patient displayed evidence of sustained elevation of serum aminotransferases during therapy with anti‐TNF. Additionally, 1 patient was observed to have a decreased HCV viral load after extended treatment with only anti‐TNF (no therapy for HCV).

Conclusion

Anti‐TNF therapy for RA in the setting of HCV appears to be safe and well tolerated without apparent influence on the underlying HCV infection. Therefore, this approach should be further evaluated prospectively for longterm safety.

     

Anti-mutated citrullinated vimentin antibodies in rheumatoid arthritis patients: Relation to disease activity and manifestations

Aim of the workTo evaluate the frequency of anti-mutated citrullinated vimentin antibodies (MCV) in rheumatoid arthritis (RA) patients and to correlate it with disease activity and various disease manifestations.Patients and methodsFifty RA patients were recruited from the rheumatology and rehabilitation outpatient clinic, Kasr Al-Aini. Thirty healthy subjects served as controls. All patients were subjected to full history taking and clinical examination including general and joint assessment. Disease activity was assessed by the disease activity score (DAS-28) and functional ability was evaluated by the Modified Health Assessment Questionnaire (MHAQ). Anti-MCV and anti-cyclic citrullinated peptide (anti-CCP) were assayed by ELISA in patients and controls. Plain X-ray was performed on the hands and wrists and Sharp score was used to assess the erosions and joint space narrowing.ResultsA highly significant elevation of serum anti-MCV in RA patients (135.82 ± 126.81 U/ml) compared to controls (13.63 ± 8.48 U/ml) (p < 0.0001) was found. Anti-MCV showed a sensitivity of 84% and specificity of 80%. There was a significant difference between anti-MCV positive and anti-MCV negative patients as regards MHAQ (1.07 ± 0.74 vs. 0.52 ± 0.37, p = 0.005) and Sharp erosion score (12.93 ± 23.55 vs. 4 ± 2.2, p = 0.02). Anti-CCP showed a sensitivity of 70% and specificity of 100%. There was a significant difference between the specificities of both markers (p = 0.03). There was no significant correlation of the anti-MCV with the clinical manifestations, MHAQ, DAS28 or Sharp score. Anti-MCV significantly correlated with anti-CCP (p < 0.0001).ConclusionAnti-MCV test has a significant association with the functional disability and radiologic progression in RA and could be considered as a promising biomarker.     

Diagnostic utility of the Elecsys anti-CCP assay in patients with rheumatoid arthritis

Abstract

Objective. The automatic anti-cyclic citrullinated peptide (anti-CCP) antibodies assay offered great advantages over traditional methods in terms of improved precision, reliability, technical simplicity, short turnaround time and high-speed throughput. In this study, we evaluated the main technical performance and diagnostic accuracy of the first automatic anti-CCP assay approved in China.

Methods. The study comprised 106 rheumatoid arthritis (RA) patients, 203 non-RA rheumatic disease controls and 46 healthy persons. Anti-CCP, rheumatoid factor (RF), α₁-acid glycoprotein, C-reactive protein and erythrocyte sedimentation rate were measured and compared. The precision, reference intervals for Chinese population and cut-off value for RA diagnosis, as well as the suitable diluent for anti-CCP were assessed. The positive rate and score of anti-CCP were compared with RF and acute-phase reactants, according to the new RA criteria.

Results. Within- and between-run imprecision, expressed as the coefficient of variation, were 0.47–1.36% and 1.15–2.63%, respectively. Upper 95% reference limit of anti-CCP in healthy Chinese was 8.8 U/mL. The area under curve of the receiver operating characteristic(ROC) for anti-CCP and RF were 0.882 (95% CI 0.833–0.930) and 0.844 (95% CI 0.792–0.897), respectively. Based on the cut-off value set by ROC, compared to RF, anti-CCP had higher sensitivity (96.8% vs. 78.3%) and specificity (90.9% vs. 70.7%). With 17 U/mL set as the optimal cut-off for anti-CCP, the total positivity of anti-CCP was comparable to that of RF (76.4% vs. 75.5%), but the high-positivity rate of anti-CCP was significantly higher (74.5% vs. 62.3%, p < 0.005).

Conclusions. Our results confirm anti-CCP as a more sensitive and specific marker than RF for the diagnosis of RA. The diagnostic performance of the Elecsys anti-CCP assay makes it a useful adjunct to clinical practice in the Chinese population.     

Histological evaluation of liver in two rheumatoid arthritis patients with chronic hepatitis B and C treated with TNF-alpha blockade: case reports

Tumor necrosis factor (TNF)-alpha antagonists successfully modulate the pathogenesis of rheumatoid arthritis (RA). However, little is known about the effect of TNF-alpha blockade on the histology of chronic viral hepatitis. We describe the cases of two patients with RA, one with concurrent chronic hepatitis B virus and the other with hepatitis C virus infection who, as part of their evaluation, underwent liver biopsies while undergoing treatment with a TNF-alpha antagonist.     

Impact of hepatitis C virus infection on disease activity,functional status and ultrasonography findings in Egyptian rheumatoid arthritis patients

Background

Hepatitis C virus (HCV) infection is one of the most frequently encountered public health problems in Egypt. It is associated with many autoimmune diseases such as rheumatoid arthritis.

Management of psoriasis patients with hepatitis B or hepatitis C virus infection

The systemic therapies available for the management of Psoriasis(PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs(c DMARDs) or biological ones(b DMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus(HBV) and hepatitis C virus(HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen(anti-HBs Ag), HBs Ag, and antibody to HCV(anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a(Cy A) or b DMARDs(etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBs Ag and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV.In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-α inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.     

Prevalence of occult hepatitis B virus infection in hemodialysis patients from egypt with or without hepatitis C virus infection

Background

While prevalence of Hepatitis B virus (HBV) in patients with end-stage renal failure (ESRF) who are undergoing dialysis has decreased significantly during the past few decades, it still remains a distinct clinical problem. The immunosuppressive nature of renal disease often leads to chronicity of the HBV infection and an opportunity for nosocomial spread of the infection among dialysis patients. Egypt is among the countries with intermediate endemicity of HBsAg (range, 2%–7%). Large-scale geographic heterogeneity in HBV prevalence has been reported worldwide and HBV prevalence is especially heterogeneous in Egypt.

Objectives

To assess the prevalence of occult HBV infection (OBI) in hemodialysis patients with or without chronic hepatitis C (HCV) from Minia and Assuit, Upper Egypt, using HBV DNA assays.

Patient and Methods

Sera from 145 hemodialysis patients with negative HbsAg were investigated for HBV DNA using real-time polymerase chain reaction (RT-PCR). Only serum samples with repeatedly detectable HBV DNA were considered positive. Patients were divided into 2 groups: HCV RNA positive and HCV RNA negative, based on the results of a third generation enzyme linked immunosorbent assay (ELISA) anti-HCV test and HCV RNA PCR.

Results

HBV DNA was detected in 6 of the 145 patients (4.1%) and HBcAb was detected in 29/145 patients (20%). There were no statistically significant differences in the age, duration of hemodialysis, biochemical parameters, serological markers of HBV, or HBV DNA between patients with and without HCV infection.

Conclusions

Four percent of the hemodialysis patients had OBI. There was no significant difference in the prevalence of OBI between hemodialysis patients with or without HCV co-infection.     

Neutralizing antibodies in hepatitis C virus infection

Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays, the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses. In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodies for control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.     

HLA-DRB1 alleles in Egyptian rheumatoid arthritis patients: Relations to anti-cyclic citrullinated peptide antibodies,disease activity and severity

BackgroundHuman leukocyte antigen HLA-DRB1 alleles encoding a common amino acid sequence called shared epitope in the third hypervariable region of DRB1 molecule have been identified as risk alleles for rheumatoid arthritis (RA).Aim of the workThe aim was to study HLA-DRB1 01, 04 and 10 alleles in Egyptian RA patients and determine their relation with anticyclic citrullinated peptide (anti-CCP) antibody level, disease activity, clinical and radiological severity.Patients and methodsThe study involved 40 RA patients and 20 control. Simplified disease activity index (SDAI) was calculated, clinical severity was assessed using the mechanical joint score (MJS) and radiological severity evaluated using the simple erosion narrowing score (SENS). HLA-DRB1 genotyping and anti-CCP antibodies were detected.ResultsThe mean patients’ age was 41.6 ± 12.7 years and disease duration 8.9 ± 7.7 years. The frequency of HLA DRB1 01, 04 and 10 in patients was 42.5%, 60% and 25% respectively. Of them 04 was significantly higher than in controls (p = 0.013) and was associated with anti-CCP positive cases (p = 0.0008) while the absence of HLA-DRB1 alleles was significantly associated with negative anti-CCP negative RA (p = 0.0008). There were significant associations between HLA-DRB1 01 and 04 with SDAI (p = 0.0002 and p = 0.005, respectively); between HLA-DRB1 04 and 10 with SENS (p = 0.002 and p = 0.001 respectively) and between HLA-DRB1 01, 04 and 10 with MJS (p = 0.02, p = 0.03 and p = 0.02, respectively).ConclusionHLA-DRB1 04 is associated with RA in Egyptian patients and is strongly associated in the production of elevated titers of anti-CCP antibodies which contribute to the development, severity and activity of the disease.     

Study of PTPN22 1858C/T polymorphism in rheumatoid arthritis patients from Western India

BackgroundRheumatoid arthritis (RA) is an inflammatory autoimmune disorder with etiologies including genetic and environmental factors. Protein tyrosine phosphatase non-receptor type22 (PTPN22) 1858C/T polymorphism is widely suspected to be a susceptibility gene for RA in the non-HLA genes group.AimThis study aimed at determining whether PTPN22 1858C/T polymorphism is associated with RA patients from Western India and to evaluate its possible association with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies.MethodsA total of 130 Indian RA patients and 100 age and sex matched normal controls were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP) for the PTPN22 1858C/T polymorphism.ResultsRF positivity was seen among 73.8% RA patients studied and the overall incidence of anti-CCP antibodies was 86.2%. The homozygous genotype (T/T) was absent in both groups. Among RF positives, C/C homozygosity was 90.6% whereas 9.4% patients were C/T heterozygous. Among anti-CCP positives, 89.1% had C/C genotype while the remaining 10.9% have the C/T genotype. Statistically significant association was obtained between the polymorphism and anti-CCP positivity in RA patients (OR: 2.939, ‘p’ value = 0.0595).ConclusionOur study suggested that a positive autoantibody status may predispose an individual to RA. PTPN22 may act as a susceptibility gene only in certain ethnic groups and there is no direct association between PTPN22 C1858 polymorphism and RA patients from Western India. Still a larger study is needed to understand whether this polymorphism predisposes individual to disease-associated antibodies among Indian RA patients.     

Anti-CCP antibodies have more diagnostic impact than rheumatoid factor (RF) in a population tested for RF

To compare the diagnostic powers of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) in a population selected for its high statistical relevance, over a 6-month period, an informed consent to test for anti-CCP was obtained from 1,025 consecutive patients for whom RF was ordered at a University laboratory. Within 1 year, a diagnosis was obtained without informing the physician about the anti-CCP result. Extensive statistical analyses were performed. A total of 768 patients satisfied the inclusion criteria, and 132 were classified as having RA, yielding a pre-test probability of RA of 17%. The sensitivities for anti-CCP and RF were 62 and 64% (P = 0.83), and the specificities were 97 and 90% (P < 0.001), respectively. The positive predictive value (PPV) was 79% for anti-CCP and 56% for RF (P < 0.001), whereas the negative predictive value was 92% for both. The likelihood ratio (LR) was 17.9 for anti-CCP and 6.2 for RF (P < 0.005). Forty RA patients were diagnosed with RA of less than 2 years length, and the same significant statistic differences between anti-CCP and RF were observed. Placing the results of both tests together, or using different cutoff points, increased the diagnostic utility of the tests. The anti-CCP test has statistically shown significant higher specificity, PPV, and LR for RA than the RF test in a clinically diverse population. If new criteria are to be devised to help diagnose early RA, anti-CCP should be included because it has a greater diagnostic impact than RF.     

Clinical relevance of antikeratin antibodies in rheumatoid arthritis

Summary Antikeratin antibodies (AKA) were found in 38 out of 96 patients with rheumatoid arthritis (RA); they appeared to be quite characteristic to this disease. There was a very low incidence of AKA positivity in the control groups, i.e., 1 out of 62 healthy subjects and 4 out of 158 other patients. With regard to the sensitivity of the test as a diagnostic tool, AKA was found to be weaker than the rheumatoid factor (RF) and the antiperinuclear factor (APF), whereas the specificity was much better than APF and RF. A clear correlation was shown between the titres of AKA and APF (p<0.001) and also between AKA levels and inflammation (p<0.02).     

Anti-neutrophil cytoplasm antibodies (ANCA) in rheumatoid arthritis: relationship to HLA-DR phenotypes,rheumatoid factor,anti-nuclear antibodies and disease severity

To investigate a possible relationship between the presence of anti-neutrophil cytoplasm antibodies (ANCA), rheumatoid factors (RF), anti-nuclear antibodies (ANA), disease severity and HLA-DR phenotypes, 46 consecutive ANCA⁺ and 48 ANCA^-, clinically well-documented RA patients were studied for RF, ANA and HLA-DR phenotypes. The 46 ANCA⁺ patients showed predominantly an atypical perinuclear staining pattern (89%). ANCA positivity was associated with higher RF titres (P<0.005) and advanced functional Steinbrocker grades III/IV (P<0.015). ANCA⁺ patients were also more often positive for ANA than ANCA^- patients (P<0.008). There was no correlation between ANCA positivity and certain HLA-DR phenotypes although the frequency of DR4⁺ (67% vs 52%) and, in particular, of DR4⁺ blanks (phenotypically homozygous) was increased in ANCA⁺ as compared to ANCA^- patients (20% vs 8%). DR4^-DR1^- RA patients were twice as frequent in the ANCA^- than in the ANCA⁺ group (22.9% vs 8.7%). Correspondingly, the DR4⁺DR1^- phenotype was increased among ANCA⁺ RA patients. Regarding functional Steinbrocker grades, the DR4⁺ phenotypes were slightly but not significantly increased in grades III and IV whereas ANCA positivity was significantly associated with severe functional Steinbrocker grades III/IV (66% ANCA⁺ vs 39% ANCA^-,P<0.015). ANCA positivity identified a population of RA patients with a long-standing and severe clinical course of the disease. There was no correlation between ANCA positivity and certain HLA-DR phenotypes.