ABSTRACT
To determine whether the presence of certain Human Leukocyte Antigen [HLA]-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies [anti-CCPAbs] and to analyze to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis [RA] in Egyptian population. Twenty nine RA patients were included in a case control study, all gave informed consents and the study was approved by the Ain Shams university ethical committee. Assessment of RA disease activity and severity was done by simplified disease activity index [SDAI] and Larsen scores respectively. Another fifteen age and sex matched subjects were also included as a control group, concentrations of anti-ccPAbs were determined in the sera of all subjects and in the synovial fluid of RA patients. The presence of HLA-DRB1 shared epitope [SE+] alleles were also determined. The alleles most strongly associated with RA susceptibility were HLA-DRB1 [01 and 04] [41.4%]. RA patients with serum anti-ccPAb titres above 60 U/ml had a higher frequency distribution of HLA-DRB1 01 [58.3%] and DRB1 04 alleles [83.3%]. There was significant positive correlation between serum and synovial anti-CCPAb titres, also between serum anti-CCPAb titres and RA disease activity and severity. HLA-DRB 1 SE+alleles [01 and 04] were strongly expressed among Egyptian RA patients. They were associated with the production of anti-CCPAb in high titres which could be involved in the disease process of RA. The presence of anti-CCPAb in high titres was associated with more active and aggressive disease. So, early determination of HLA-DRB 1 SE+alleles and serum anti-CCPAb titre in RA patients could facilitate the prediction of disease course and prognosis at the time of initial presentation
Subject(s)
Humans , Male , Female , HLA-D Antigens/blood , Peptides, Cyclic/blood , Disease Progression , PrognosisABSTRACT
Spondyloarthritis [SpA] are a group of seronegative inflammatory arthritis targeting the axial skeleton with or without peripheral asymmetrical oligoarthritis. Specific laboratory markers for SpA have been lacking Anti-Saccharomyces cerevisiae antibodies [ASCA], a known serological marker for Crohn's disease [CD], it is directed to the cell wall man-nan of Saccharomyces cerevisiae, commonly known as baker's yeast. We aimed at investigating patients with SpA and its different subgroups for the presence of ASCA-IgA antibodies and to assess its clinical significance if any, in comparison to inflammatory and healthy controls. In this study we examined 31 patients with different spondyloarthritis. They were diagnosed and classified according to the European Spondyloarthritis Study Group [ESSG] criteria: seven patients with Ankylosing Spondylitis [AS], 6 patients with Reactive arthritis [ReA], 3 patients with enteropathic arthritis [EA] 10 patients with psoriatic arthritis [PsA] and 5 with undifferentiated Spondyloarthritis [uSpA].Ten patients with Rheumatoid Arthritis [RA], diagnosed according to the American College of Rheumatology revised criteria were included as an inflammatory control group, in addition to 10 age and sex matched volunteers as a healthy control group. Full history taking and thorough physical examination including detailed muscloskeletal evaluation, with clinical assessment of disease activity using the Bath Ankylosing Spondylitis Disease Activity Index [BAS- DAI] were done. Routine laboratory investigations, ESR, C-reactive protein [CRP] and rheumatoid factor [RF] were also evaluated. Plain X ray and computed tomography [CT] scan on sacroiliac joints and the spine were done to SpA patients, according to the New York grading scale. ASCA-IgA levels were assayed by enzyme linked immunosorbent assay [ELISA]. ASCA-IgA level was significantly higher [P < 0.01] in SpA patients [51.96U/ml] than that of either RA patients [22.80U/ml] or controls [10.90U/ml]. The highest level of ASCA antibodies were found in EA subgroup [131.33U/ml], followed by AS [62.57U/ml], than in uSpA [52.00U/ ml], next in Re A [28.00U/ml] and the lowest value was found in PsA [23.83U/ml]. There was non significant difference [P > 0.05] regarding ASCA-IgA level between RA patients and controls. We have 11/31 [35.5%] SpA patients who previously underwent iliocolonoscopy for various reasons, they have clinical or subclinical bowel inflammation, when their mean ASCA-IgA level [85.36U/ml] was compared to that of other SpA patients [36.25U/ml] the difference was highly significant [P < 0.01]. ASCA-IgA was correlated positively with ESR, CRP and BASDAI score [r = 0.531, 0.625 and 0.705] respectively, while it was negatively correlated with age of the patients [r = -0.529]. Receiver operator characteristic curve [ROC] was obtained for ASCA-IgA, the best cut off value for ASCA-IgA in diagnosing SpA was found to be at 27.0 U/ml at which its sensitivity was [74%] and specificity was [95%]. Meanwhile, non significant correlation was found between ASCA-IgA level and radiologically evidenced sacroiliitis in SpA patients. ASCA-IgA antibodies detected by simple ELISA test were found to be of a significant diagnostic value in SpA patients, especially those with EA, AS and uSpA. It is of a high specificity [95%] and sensitivty [74%] at cut off value 27.0 U/ml. It is a sensitive marker in reflecting SpA disease activity, as it is well correlated with clinical and laboratoy markers of disease activity. So, ASCA-IgA might be a helpful marker for disease follow up and monitoring the patient's response to therapy. Additionally, it is well correlated with the presence of clinical or preclinical bowel inflammation. However, extended follow up studies are needed on SpA patients specially those with high ASCA-IgA level to know whether some would progress to frank inflammatory bowel disease [IBD] or not and could ASCA be regarded as a potential risk factor in this progression, need to be evaluated