Influence of human leucocyte antigen HAL-DRB1 and anti-cyclic citrullinated peptide antibodies on rheumatoid arthritis patients

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

Use of anti-cyclic citrullinated peptide antibodies to distinguish between rheumatoid arthritis and hepatitis C virus infection associated polyarthritis

Hepatitis C is a major health problem in Egypt, the prevalence of HCV infection ranges from 15% to 20%.The presence of extrahepatic manifestations is a relatively common feature in patients with chronic hepatitis C virus [HCV] infection. Among the different clinical disorders associated with HCV infection, articular involvement is a frequent complication, and the clinical picture of HCV-related arthropathy varies widely. In clinical practice differentiating patients with HCV-related polyarthritis from patients with rheumatoid arthritis [RA] represents both a diagnostic and a therapeutic challenge. It is to assess the utility of anti-cyclic citrullinated peptide [anti-CCP] antibodies in distinguishing between patients with rheumatoid arthritis [RA] and patients with chronic hepatitis C virus [HCV] infection associated polyarthritis who are seropositive for rheumatoid factor. The study included 66 subjects divided as follows: Group [1]: 21 patients with RA fulfilling the ACR criteria, all were seropositive for RF and negative for HCV infection. Group [2]: 8 patients with chronic HCV infection and RA fulfilling the ACR criteria, all were seropositive for RF. Group [3]: 11 patients with HCV undifferentiated polyarthralgia or arthritis, all were seropositive for RF. Group [4]: 10 patients with HCV infection without articular involvement. Group [5] 16 age and sex matched healthy controls. HCV infection had been diagnosed on the basis of the presence of anti-HCV antibodies as detected by third generation ELISA and confirmed by the detection of viral RNA in serum by PCR technique. Anti-CCP was measured by second-generation [ELISA], the positive cut off value>20 units. The statistical study was carried out by the Chi2, Fisher, Student's t and Mann-Whitney tests. Anti-CCP was detected in 16/21 patients with RA group-l [76%], 7/8 patients with HCV and RA group-2 [87.5%], 3/11 patients with HCV undifferentiated arthropathy group-3 [27%] and 1/10 patients with HCV group-4 [10%].Anti-CCP was not found in the sera of the healthy controls. Anti-CCP was significantly higher in RA patients group-1 compared to HCV arthropathy patients group-3 and HCV patients without arthritis group-4 [p<0.05], also it was significantly higher in HCV and RA patients group-2 compared to HCV arthropathy patients group-3 and HCV patients group-4 [p

Anti saccharomyces Cerevisiae antibodies [ASCA], a promising marker in spondyloarthropathies

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

Efficacy of cystatin C as a screening test for reduced glomerular filtration rate

The objective of this study was to evaluate the efficacy of cystatin C as a screening test for reduced glomerular filtration rate [GFR] in comparison to S. creatinine and to assess whether cystatin C is performed differentially in either glomerular or tubular renal diseases or not. This study involved 105 patients with different renal diseases they were admitted as inpatients in Internal Medicine Department at Ain Shams University Hospital, and were classified according to GFR ml/min/1.73 m[2] into : group I patients, n = 35, GFR >/= 70 ml/min/1.73 m[2] group II patients, n = 33, GFR [< 70 - >/= 50] ml/mins/1.73m[2] and group III patients, n= 37, GFR < 50ml/min/1.73m[2], and a control group of 30 volunteers with matched age and sex to evaluate the reference value of cystatin C. All groups were subjected to the following : complete history taking and thorough clinical examination. Kidney function tests including : Bun, S. creatinine, creatinine clearance, 24 hours urinary proteins quantitation, [99m]Tc DTPA renal isotope scanning for accurate evaluation of glomerular filtration rate [GFR]. Abdominal U/S with full comment on the kidneys. Qualitative assessment of urinary proteins. Assessment of serum cystatin C by DAKO cystatin C pet kit which is particle enhanced turbidimetric immunassay. Our results revealed that the mean S. cystatin C was 7.9 +/- 3.8, 14.3 +/- 8.2 and 16.2 +/- 3.6 mg/l in groups I, II and III respectively when compared with that of the control group with a mean of 0.9 +/- 1 mg/l it was statically highly significant [F = 61.8, P < 0.01]. S. cystatin C was more sensitive than S. creatinine in reflecting the true GFR, this was specially observed in group I patients [mild renal impairment] as their mean serum creatinine was still within its normal range 0.97 +/- 0.4 mg/dl, while their mean GFR measured by both creatinine clearance and isotope clearance was 68.3 +/- 4.7, 67.5 +/- 45 ml/min/1.73 m[2] respectively. Meanwhile, their mean S. cystatin C was 7.9 +/- 3.8 mg/l statistically highly significant than that of the control group with a mean of 0.9 +/- 1 mg/l, [P < 0.05]. Also there was statistically non significant correlation between S. cystatin C and S. creatinine in group I patients [r = 0.1, P > 0.05] while there was significant correlation between them in group II and III patients [r = 0.38, 0.59, P < 0.05]. Moreover, S. cystatin C has a significant negative correlation with GFR measured by both creatinine clearance [r = -0.37, -0.54 and -0.48] and radioisotope clearance [r = -0.34, -0.35 and -0.37], [P < 0.05] in groups I, II and III respectively, i.e., throughout the whole range of renal impairment. Cystatin C had non significant correlation with either age or sex of the patients. While, S. creatinine had a significant correlation with creatinine clearance and isotope clearance in group II and III patients, i.e., with advanced renal diseases, but not with group I patients [mild renal impairment]. Also S. cystatin C had higher sensitivity [90% [vs] 83%] and negative predictive value [NPV] [89 [vs] 80] than S. creatinine in assessing GFR measured by both creatinine clearance or by radioisotope clearance. There was non significant difference regarding the mean S. cystatin C between subgroup [A] [glomerular diseases] and subgroup [B] [tubular diseases] within the same GFR category [P > 0.05]. S. cystatin C was more sensitive and superior to S. creatinine in detecting reduced GFR measured by both creatinine and radioisotope clearance. S. cystatin C is more efficacious than S. creatinine as a screening test as it had a higher sensitivity and higher negative predictive values than S. creatinine. In detecting reduced GFR. The efficacy of cystatin C is independent on either glomerular or tubular renal diseases and showed a high degree of reproducibility