Rheumatoid Factor, Anti-cyclic Citrullinated Peptide and HLA-B Locus Antigens in Psoriatic Arthritis Patients in Bangladesh

Introduction: Psoriatic arthritis (PsA) is established as a multifactorial disease resulting from a complex interplay between genetic, environmental and immunological factors. It is a seronegative arthritis but rheumatoid factor may be present in up to 15% of PsA patients Antibodies recognizing a cyclic citrullinated peptide are highly speciûc for rheumatoid arthritis (RA) but their role in PsA remains unclear. An increased prevalence of anti-CCP antibody in PsA is also reported. Study shows that HLA-DRB1 shared epitope is signiûcantly associated with the presence of anti-CCP antibody in PsA patients but this type of association is not found with other human leukocyte antigens. Objectives: The aim of this study was to investigate the frequency of anti-CCP and RF in PsA patients and their associations with HLA-B locus antigens. Methods: In this cross sectional study, we selected 50 unrelated consecutive patients with PsA according to CASPAR criteria for PsA. 6 ml of blood was collected from each patient for HLAB locus typing, RA test and test for anti-CCP. Patient’s serum samples were tested for RF by Nephelometric system and tests for anti-CCP were done by ELISA. HLA-B locus typing was done by PCR with sequence specific primer. Results: Among 50 PsA patients, 27 (54%) are female and 23 (46%) are male. RA test is positive in 10 (20%) patients and anti-CCP is positive in 7 (14%) patients. Significant association was found between HLA-B*37 and RF (p value= < 0.001). Conclusion: RF is present in 10 (20%) and anti-CCP is present in 7 (14%) PsA patients. HLAB* 37 was significantly found in RF positive patients. J Shaheed Suhrawardy Med Coll 2020; 12(2): 109-114

Study the Role and Value of Antibodies to Cyclic Citrullinated Peptide in Early Rheumatoid Arthritis

Research relevance: prognosis of early rheumatoid arthritis (RA) course remains an unresolved problem, which dictates the need to identify new factors affecting the activity and course of the disease. Research objectives: it is assumed that the cause of immunopathological reactions in early RA is a dysregulation of the immune response resulting from an imbalance in the function of T- and B-lymphocytes, namely, the immunodeficiency of the T-lymphocyte system, which leads to uncontrolled synthesis of immunoglobulins by B-lymphocytes, in particular, organo- and tissue-specific antibodies. Research methods: this article analyzes occurrence frequency, pathogenetic and clinical significance of antibodies to cyclic citrullinated peptide (ACCP) in early rheumatoid arthritis (RA). Research results: in this work, in patients with early RA, the detection rate of ACCP was 68.8%, the frequency of detection of ACCP was higher than that of rheumatoid factor. Conclusions: in the examined patients with early RA, the presence of ACCP did not depend on gender and age but depended on the duration of the disease.

OTOİMMÜN ROMATOİD HASTALIKLARDA OTOANTİKORLAR

The diagnosis of autoimmune rheumatoid diseases can be made by combining parameters consisting of clinical, histopathological, laboratory and immunological tests. Among these parameters, autoantibodies are of great benefit in differential diagnosis, especially for patients with unclear clinical data. Immunofluorescence, ELISA, immunodiffusion, immunoprecipitation and Western blot can be used to identify autoantibodies. While autoantibodies like antinukleer antibody, double stranded deoksiribonukleic asid and anti neutrophils antibody are detected by immunofluorescence as a golden standard test, Anti-cyclic Citrullinated Peptide Antibody (CCP), antiphospholipid antibodies (anti-cardiolipid) are evaluated by ELISA and ENA group by immunoblot or western blot. Today the number of autoantibodies that can be detected is over 100. The indication of some of these autoantibodies are not known even today. The definition of antinuclear antibody group autoantibodies plays a crucial role for the diagnosis and treatment of systemic and organ-specific illnesses. With these methods, practical, fast and trustworthy results in clinical medicine and clinical immunology can be obtained.

Diagnostic value of anti-cyclic citrullinated peptide antibody combined with rheumatoid factor in rheumatoid arthritis in Asia: a meta-analysis

Objective This meta-analysis explored the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor (RF) for rheumatoid arthritis (RA) in the Asian population. Methods Embase, Medline, Cochrane Library, Chinese Science and Technology Periodicals, China National Knowledge Infrastructure, and China Wanfang Databases were searched from 1 January 2000 to 1 February 2021 to collect studies on the combined detection of anti-CCP and RF for diagnosing RA. The sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (−LR) were combined and analyzed. Summary receiver operating characteristic (SROC) curves were drawn. Results Twenty-four published papers were analyzed, including 21 combined in series and 8 combined in parallel. In the tandem analysis, the sensitivity = 0.64 [95% confidence interval (CI): 0.58–0.70], specificity = 0.97 (95%CI: 0.95–0.98), +LR = 19.70 (95%CI: 12.74–30.46), −LR = 0.37 (95%CI: 0.31–0.43), DOR = 53.43 (95%CI: 34.46–82.40), and area under the SROC curve = 0.89. In the parallel combination, the sensitivity = 0.87 (95%CI: 0.80–0.92), specificity = 0.76 (95%CI: 0.67–0.84), +LR = 3.68 (95%CI: 2.62–5.17), −LR = 0.17 (95%CI: 0.11–0.26), DOR = 21.56 (95%CI: 11.63–39.99), and area under the SROC curve = 0.89. Conclusion Anti-CCP and RF combined detection improves the diagnostic efficiency of RA, providing a potential strategy for early clinical screening in the Asian population. This trial was retrospectively registered in the INPLASY/Research Registry ( https: //inplasy.com/ ) with the registration number INPLASY202180106.

Specificity of Anti-Citrullinated Protein Antibodies to Citrullinated α-Enolase Peptides as a Function of Epitope Structure and Composition

Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1–2% of the world population. In addition to the first discovered serologic markers for RA, the rheumatoid factors (RFs), anti-citrullinated protein antibodies (ACPAs) are even more specific for the disease compared to RFs and are found in 70–80% of RA patient sera. RA etiopathogenesis still needs to be elucidated, as different factors are proposed to be involved, such as Epstein–Barr virus infection. Hence, understanding the interaction between ACPAs and their citrullinated peptide targets is relevant for a better knowledge of RA pathophysiology and for diagnostic purposes. In this study, a cohort of RA sera, healthy control sera and multiple sclerosis sera were screened for reactivity to a variety of citrullinated peptides originating from α-enolase, pro-filaggrin, proteoglycan and Epstein–Barr nuclear antigen-2 by enzyme-linked immunosorbent assay. ACPA reactivity to citrullinated α-enolase peptides was found to depend on peptide length and peptide conformation, favouring cyclic (disulfide bond) conformations for long peptides and linear peptides for truncated ones. Additional investigations about the optimal peptide conformation for ACPA detection, employing pro-filaggrin and EBNA-2 peptides, confirmed these findings, indicating a positive effect of cyclization of longer peptides of approximately 20 amino acids. Moreover, screening of the citrullinated peptides confirmed that ACPAs can be divided into two groups based on their reactivity. Approximately 90% of RA sera recognize several peptide targets, being defined as cross-reactive or overlapping reactivities, and whose reactivity to the citrullinated peptide is considered primarily to be backbone-dependent. In contrast, approximately 10% recognize a single target and are defined as nonoverlapping, primarily depending on the specific amino acid side-chains in the epitope for a stable interaction. Collectively, this study contributed to characterize epitope composition and structure for optimal ACPA reactivity and to obtain further knowledge about the cross-reactive nature of ACPAs.

Identification of genetic loci associated with antibodies to specific sets of citrullinated peptides in rheumatoid arthritis patients

Objectives: Production of anti-citrullinated peptide/protein antibodies (ACPA) is characteristic for rheumatoid arthritis (RA) and may inform about biological pathways involved in disease development in specific subgroups. Since multiple loci in genome wide association screens have been implicated in RA risk, we investigated the association between genetic variations and the development of multiple types of ACPA in three big cohorts of RA patients from Sweden, USA and UK (EIRA, NARAC and WTCCC) with overall 6,127 individuals with RA. Methods: We combined genotyping data from Illumina Immunochip with serological data for 16 ACPA specificities from a custom-made multiplex microarray (Thermo Fisher Scientific, ImmunoDiagnostic division). A logistic regression-based association test in each cohort was followed by meta-analysis. Results: We report several loci, harbouring three or more variants associated with ACPA, reaching study-wide significance (FDR<0.1) -PTPN22, LINC02341_TNFSF11, THADA and TMEM174. Most of these loci are not known to be associated with RA. Stratification by shared epitope (SE) alleles indicated an association between the PTPN22 locus and levels of antibodies binding to the vimentin peptide, Cit-Vim60-75, in SE positive cases, but not in SE negative cases. Conclusion: Our data identifies several new loci which associate with subsets of RA characterized by presence of specific ACPA and indicate unknown disease heterogeneity.