Association of complement factor B allotypes and serum biomarkers in rheumatoid arthritis patients and their relatives

Abstract

The aim of the study was to investigate the allotypic variability of complement factor B (BF) in patients and relatives with rheumatoid arthritis (RA) and its association with serological biomarkers and clinical features of the disease. BF allotypes were determined by high-voltage agarose gel electrophoresis in serum samples of 180 patients with RA, 198 relatives and 98 controls from Southern Brazil. Anticyclic citrullinated peptide (anti-CCP), antimutated citrullinated vimentin (anti-MCV) and IgA-rheumatoid factor (RF) were determined by ELISA and IgM-RF by latex agglutination in all samples. No significant differences were found in the allotypic variants of BF between patients with RA, relatives and controls, nor associations with gender and age of RA onset. BF*S07 allotype was significantly associated with extra-articular manifestations (EAMs; Secondary Sjögren Syndrome, pneumonitis, rheumatoid nodules) in patients with RA (P = 0.02; OR = 6.62). Patients with phenotype BF F had lower positivity for anti-MCV biomarker (P = 0.02; OR = 0.22) and those with allotype BF*S had higher prevalence of this autoantibody (P = 0.02; OR = 3.77). An increased frequency of RF-IgA was detected in relatives of patients with RA with BF FS07 phenotype (P = 0.02; OR = 7.78). Complement BF variability did not influence the development of RA in the studied patients, but BF variants may act as markers of disease prognosis, such as development of EAMs, corroborating with the role of the alternative pathway in the pathogenesis of RA.

Potential clinical biomarkers in rheumatoid arthritis with an omic approach

“…Considered useful in early stages of the disease to predict the development of erosions and the presence of the IgA isotype is associated with extra-articular manifestations. Aggressive development of the disease and decreased response to anti-TNF therapy have been reported at high levels [ 42 , 53 , 57 , 68 , 74 , 75 , 99 , 109 , 121 , 124 ] PHASE 1 Anti-citrullinated protein antibodies (ACPA) Non-omics Biomarker more sensitive (60–80%) and specific (95–98%) for the diagnosis of RA than RF. ACPA + patients develop a more aggressive and erosive progressive disease clinical phase compared to ACPA- patients; Positivity has been associated with a better response to treatment in early stages but medication-free remission is less frequent.…”

“…Baseline levels can be predictive for the response to methotrexate and ACPA + subjects are associated with a better response to abatacept independent of disease activity. It has been detected in healthy patients therefore increases the risk of developing RA by 5% in the next 5 years [ 42 , 51 , 53 – 57 , 65 , 68 , 74 , 75 , 99 , 109 , 110 , 112 , 121 ] PHASE 1 Anticarbamylated protein (anti-CarP) antibodies Non-omics Association with rapid radiological damage and severe course of the disease independent of the ACPA value. In patients ACPA—it is associated with the development of arthralgias [ 57 , 65 , 74 , 109 , 112 ] PHASE 1 Regulatory B lymphocytes (Breg) Non-omics Protective role in RF + patients (Lower T2/Breg levels) [ 62 ] PHASE 1 Erythrocyte Sedimentation Rate (ESR) Non-omics Nonspecific indicator of the amount of inflammation in the elevated body in patients with RA.…”

“…(precision 93% y 95% in RA patients) [ 52 ] PHASE 2 Anti-mutated citrullinated vimentin (anti-MCV) Non-omics Significant correlation with ACPA (r = 0.73). comparable value to ACPA for RA early diagnosis, with lower sensitivity and specificity [ 54 , 99 ] PHASE 3 MicroRNAs (miRNAs): miR 223‐3p and miR 16‐5p Epigenomics Prediction of disease outcome in eAR [ 43 ] PHASE 3 miR-642b-5p, miR-483-3p, miR-371b-5p (up-regulated) and miR-25-3p, miR-378d (down-regulated) Epigenomics Association with devolopment RA in undifferentiated arthritis patients after 4 years [ 46 ] PHASE 3 Hypo-methylation in 4 genes (FCRLA, CCDC88C, BCL11B and APOL6) Epigenomics Association with RA progression [ 50 ] PHASE 3 M1V variant SNP (rs3764880, A>G) Genomics Association with good activity of disease and classifies patients that require less therapeutic interventions [ 58 ] PHASE 3 Genetic variant (rs7607479) of the SPAG16 gene Genomics Protective role for radiological progression [ 91 ] PHASE 3 BF*S07 allotype of complement factor B Genomics Significantly associated with extra-articular manifestations (EAM) in brazilian RA patients [ 99 ] PHASE 3 B cell antigen receptor complexassociated protein alpha chain (CD79A) Proteomics Correlation with joint destruction [ …”

Risk Factors Analysis for the Development of Hypocomplementemia in Rheumatoid Arthritis Patients: A Single-Center Retrospective Study

“…The complement system is a main constituent within human immune system, and inadequate control of complement activation constitutes the formation of the pathogenesis of inflammatory and autoimmune diseases, containing RA. 4 , 5 The classical and lectin pathways of the complement system may involve in vasculitic neuropathy related to RA and systemic lupus erythematosus (SLE). 6 The complement system involved in the pathogenesis of RA acts only on localized mucous in the preclinical stage, whereas it acts on joints and system in RA patients with clinically significant arthritis.…”