Next-generation rheumatoid factor assay provides improved predictive power for the development of arthritis in patients at risk.

OBJECTIVE: Rheumatoid arthritis (RA) is characterised by the presence of autoantibodies, among which those targeting the constant region of immunoglobulin G (IgG), called rheumatoid factors (RF). Despite this link, RFs can also be found in other disorders and the healthy population, which hampers its use as a diagnostic tool. We recently showed that a subset of RA-derived RFs target a distinct epitope on the IgG-Fc, a feature that is currently not used in the clinic. METHODS: We determined immunoglobulin M (IgM)-RF levels specific against an RA-associated epitope (using our engineered next-generation RF antigen 'T3-17') in a prospective cohort of 475 patients with seropositive (for IgM-RF or aCCP) arthralgia that were followed for 5 years or until the development of arthritis. RESULTS: The presence of RFs targeting T3-17 was more strongly associated with progression to arthritis in comparison to traditional RF measurements. Within the group of patients positive for T3-17 RF the risk of arthritis development was increased as compared with wild-type RF, HR=3.2 (95% CI 2.4 to 4.3) vs HR=2.2 (95% CI 1.7 to 3.0). Predictive power of T3-17 RF was improved in combination with aCCP titres, HR=6.4 (4.7-8.7) vs HR=5.1 (3.9-6.8). This combination performed better than aCCP detection on its own. CONCLUSION: The detection of disease-specific RF is feasible and seems to improve the diagnostic power of RF and should be considered to be implemented in the clinic.

Complete Description of the Three Pathways of the Complement System in a Series of 430 Patients with Rheumatoid Arthritis.

The complement (C) system is implicated in the etiopathogenesis of rheumatoid arthritis (RA). However, there is a lack of studies characterizing all three C pathways in RA patients. This study aimed to evaluate the association between an in-depth examination of the C system and RA patient characteristics, focusing on disease activity and the presence of rheumatoid factor and anti-citrullinated protein autoantibodies (ACPA). In a cohort of 430 RA patients, functional assays of the three C pathways (classical, alternative, and lectin) and serum levels of their components were assessed. Components included C1q (classical); factor D and properdin (alternative); lectin (lectin); C1-inhibitor; C2, C4, and C4b (classical and lectin); C3, C3a, and C4b (common); and C5, C5a, and C9 (terminal). A multivariable linear regression analysis showed significant positive correlations between C-reactive protein and C system proteins and functional assays, especially in the terminal and common pathways. Disease activity, measured by scores with or without acute phase reactants, positively correlated with the classical pathway functional test and terminal pathway products. Conversely, rheumatoid factor or ACPA presence was associated with lower classical pathway values and decreased C3a and C4b levels, suggesting complement depletion. In conclusion, RA disease activity increases C molecules and functional complement assays, while rheumatoid factor or ACPA positivity is linked to C consumption. Our study offers a detailed analysis of the complement system's role in RA, potentially guiding the development of more targeted and effective treatment strategies.

[High expression of anti-ß2 glycoprotein I (ß2GPI) autoantibody exacerbates inflammation and immune dysfunction in connective tissue disease].

Objective To observe the expression of anti-ß2 glycoprotein I (ß2GPI) autoantibody in connective tissue diseases and its relationship with the degree of inflammation and immune function. Methods Patients with broad connective tissue diseases including connective tissue disease (CTD), rheumatoid arthritis (RA), Sjogren's syndrome (SS), and systemic lupus erythematosus (SLE) were observed. ß2GPI was quantified by chemiluminescence, ESR was measured by Weil's method, and C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated polypeptide (CCP) antibody were measured by automatic biochemical analyzer. Results ß2GPI and their subtypes were significantly higher in RA patients compared with CTD, SS, and SLE patients. CRP was positively associated with anti-ß2GPI antibody and anti-ß2GPI antibody IgM in patients with connective tissue disease. ESR was positively associated with anti-ß2GPI antibody. Anti-ß2GPI antibody and anti-ß2GPI antibody IgM were elevated in the abnormal CRP group compared with the normal CRP group. Compared with the ESR normal group, anti-ß2GPI antibody and anti-ß2GPI antibody IgG were elevated in the ESR abnormal group. Anti-ß2GPI antibody was positively correlated with ESR and anti-CCP antibody in RA patients. Anti-ß2GPI antibody IgG was positively correlated with RF. Conclusion ß2GPI can be used as a predictor of the degree of inflammation and assessment of immune disorders in CTD.

[Clinical characteristics and labial gland pathological features in children with systemic lupus erythematosus complicated by Sjögren's syndrome]. / å„¿ç«¥ç³»ç»Ÿæ€§çº¢æ–‘ç‹¼ç–®åˆå¹¶å¹²ç‡¥ç»¼åˆå¾çš„ä¸´åºŠç‰¹ç‚¹åŠå”‡è ºç— ç†ç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical manifestations, laboratory features, and labial gland pathological features in children with systemic lupus erythematosus (SLE) complicated by Sjögren's syndrome (SS). METHODS: A retrospective analysis was conducted on 102 children with SLE who underwent labial gland biopsies at Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2022. The children were divided into two groups based on the presence of SS: the SLE with SS group (SLE-SS; 60 children) and the SLE-only group (42 children). According to the focus score (FS) of the labial glands, children in the SLE-SS group were further subdivided into FS≥4 subgroup (26 children) and FS<4 subgroup (34 children). The clinical data of the groups were compared. RESULTS: Compared to the SLE-only group, children in the SLE-SS group had less skin and mucosal involvement, were more likely to have positive anti-SSA and anti-SSB antibodies, and had higher levels of rheumatoid factor (P<0.05). There was no significant difference in treatment protocols between the two groups (P>0.05). Compared to the FS<4 subgroup, the FS≥4 subgroup had more frequent musculoskeletal involvement (P<0.05), but there was no significant difference in SLE disease activity or other major organ involvement between the subgroups (P>0.05). CONCLUSIONS: Children with SLE complicated by SS are less likely to have skin and mucous membrane involvement and exhibit specific serological characteristics. The SLE-SS children with an FS≥4 are more likely to experience musculoskeletal involvement. However, FS is not associated with disease activity or other significant organ damage.

Differences in referral path, clinical and radiographic outcomes between seronegative and seropositive rheumatoid arthritis Mexican Mestizo patients: A cohort study.

BACKGROUND: The study compared the referral path, the first two-year clinical outcomes, and the first five-year radiographic outcomes between seronegative patients (SNPs) from a recent-onset rheumatoid arthritis dynamic cohort initiated in 2004 and seropositive patients (SPPs). Predictors of incidental erosive disease were investigated. PATIENTS AND METHODS: Up to March 2023, one independent observer reviewed the charts from 188 patients with at least two years of clinical assessments and up to five years of annual radiographic assessments. SNPs were defined when baseline RF and ACPA serum titers were within local normal ranges. The erosive disease was defined on hand and/or foot radiographs when at least one unequivocal cortical bone defect was detected. The incidental erosive disease was defined in baseline erosive disease-free patients who developed erosions at follow-ups. Multivariate Cox regression analyses identified hazard ratios (95% confidence interval) for factors to predict incidental erosive disease. RESULTS: There were 17 (9%) SNPs, and they had a shorter time from symptoms onset to first physician evaluation, visited a lower number of physicians, and received less intensive treatment at referral and during the first years of follow-up than SPPs. Also, they had fewer 0-66 swollen joints and were less frequently persistent on therapy. The erosive disease was detected only in SPPs, and its frequency increased from 10.1% at baseline to 36.1% at the five-year radiographic assessment. There were 53 (31.4%) patients with incidental erosive disease, and differences between SPPs and SNPs were statistically significant at the feet location. Incidental erosive disease was predicted by baseline ACPA, ESR, substantial morning stiffness, and cumulative CRP. CONCLUSIONS: SNPs showed mild differences in their referral path and clinical outcomes compared to SPPs. However, erosive disease was detected only in SPPs and was predicted by baseline and cumulative clinical and serologic variables.

A Case of False Elevation of D-Dimer and Elimination Methods.

BACKGROUND: There are many methods for the detection of D-dimer in clinical laboratories. Immunoturbidimetric assays are widely used because of its high sensitivity and specificity [1-3]. However, this method may be affected by the interference of rheumatoid factor (RF), heterophilic antibodies, and other unknown proteins, and its falsity will increase, thus affecting clinical diagnosis. METHODS: This paper reports the cause analysis of a case of spurious D-dimer increase and four corresponding elimination methods: double dilution of the original specimen, detection of fibrin degradation product (FDP) level, addition of heterophilic blocking reagent, and comparison between different instruments. RESULTS: It was confirmed that there were special antibodies in the patient's body by four methods, which had non-specific reactions with D-dimer reagents, resulting in false increases of results. CONCLUSIONS: When the coagulation function results of patients show isolated increases in D-dimer, or the results are inconsistent with clinical symptoms, laboratory personnel should consider the possibility of interference factors, and conduct effective treatment to obtain correct test results, and thus reduce the occurrence of medical adverse events caused by inaccurate test results.

Case of isolated scleromalacia perforans with seropositivity for rheumatoid arthritis.

Scleromalacia perforans, or necrotising anterior scleritis, is a rare and severe form of eye disease that usually occurs in patients suffering from long-standing systemic inflammatory diseases, with rheumatoid arthritis (RA) being the most common. Here, we report the case of a patient who presented with redness of the eye and discolouration of the sclera and was diagnosed with scleromalacia perforans without any further extraophthalmic systemic involvement. Serological workup revealed highly positive cyclic citrullinated peptide (CCP) antibody (CCP-IgG/anticitrullinated protein antibodies) and positive rheumatoid factor, serologies commonly associated with RA. The patient's symptoms responded very well to rituximab therapy.

[Regulatory effect of lactate on peripheral blood CD4+ T cell subsets in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the serum lactate level in patients with rheumatoid arthritis (RA) and its relationship with disease activity, and to analyze the effect of sodium lactate on the activation of CD4+ T cells, the ability of secreting cytokines and CD4+T cell subsets in peripheral blood of the RA patients. METHODS: The peripheral blood of healthy controls (HC) and RA patients was collected, and the content of lactate in the supernatant was detected by lactate detection kit, the correlation between the content of lactate and the disease score of the RA patients was analyzed; the activation level of CD4+ T cells, the proportion of CD4+ T cell subsets and the cytokines secreted by CD4+ T cells in peripheral blood of all the RA patients were detected by flow cytometry after being stimulated with sodium lactate. RESULTS: The serum lactate level in the RA patients (n=66) was significantly higher than that in the HC (n=60, P < 0.001), and there was a certain correlation with disease activity score in 28 joints (DAS28)-C-reactive protein (CRP) (r=0.273, P=0.029), The levels of rheumatoid factor [RF, 197.50 (26.03, 783.00) IU/mL vs. 29.30 (0.00, 102.60) IU/mL, P < 0.01], CRP [37.40 (11.30, 72.60) mg/L vs. 5.83 (2.36, 12.45) mg/L, P < 0.001], were increased in patients with the lactate concentration greater than 5 mmol/L were significantly higher than those in patients with the lactate concentration less than or equal 5 mmol/L, however, there was no significant difference in the expression of erythrocyte sedimentation rate [ESR, 42.00 (19.00, 77.00) mm/h vs. 25.00 (12.50, 45.50) mm/h, P>0.05] and anti-cyclic citrullinated peptied (CCP) antibody [82.35 (17.70, 137.00) RU/mL vs. 68.60 (25.95, 119.70) RU/mL, P>0.05]. Compared with the control group, the expression of PD-1 (46.15%±8.54% vs. 41.67%±9.98%, P < 0.001), inducible costimulatory molecule (ICOS, 5.77%±8.60% vs. 18.65%±7.94%, P < 0.01) and CD25 (25.89%±5.80% vs. 22.25%±4.59%, P < 0.01) on the surface of CD4+ T cells in the RA patients treated with sodium lactate was significantly increased. Compared with the control group, the proportion of Th17 (4.62%±1.74% vs. 2.93%±1.92%, P < 0.05) and Tph (28.02%±6.28% vs. 20.32%±5.82%, P < 0.01) cells in CD4+T cells of the RA patients in the sodium lactate treatment group increased. Compared with the control group, the expression of IL-21 (5.73%±1.59% vs. 4.75%±1.71%, P < 0.05) in CD4+T cells was up-regulated in the RA patients treated with sodium lactate. CONCLUSION: The level of serum lactate in RA patients is increased, which promotes the activation of CD4+T cells and the secretion of IL-21, and up-regulates the proportion of Th17 and Tph cells in the RA patients.

Effect of Disease-related Variables on Bone Mineral Density in Patients with Rheumatoid Arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the bony architecture. Nevertheless, it remains uncertain whether these effects are due to disease progression, limited mobility, or medication. We conducted this study to analyze changes in bone mineral density (BMD) in patients with RA and its relationship with various disease parameters, such as demographic factors, disease activity, functional disability, duration since onset of symptoms, cumulative steroid dose, and titers of rheumatoid factor (RF). MATERIALS AND METHODS: This cross-sectional study was conducted at the Rheumatology Clinic of the Tertiary Care Hospital of Mumbai. We included 96 consecutive patients diagnosed with RA using the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. Demographic, clinical, and biochemical data were also collected. Disease severity was assessed using the Disease Activity Score 28 with Erythrocyte Sedimentation Rate (DAS28-ESR) score, and physical disability was assessed using the Health Assessment Questionnaire (HAQ) score. BMD was calculated using dual-energy X-ray absorptiometry (DEXA). Significant variations among continuous variables were examined using the t-test, while disparities between categorical variables were evaluated using the Chi-squared test. Statistical significance was set at p < 0.05 within the 95% confidence interval (CI) range. RESULTS: Of the 96 patients, 77 were female, and 19 were male. The mean age of the study population was 45.28 ± 10.15 years. As the age of patients increased, BMD was found to decrease in the total lumbar spine, neck of the femur, and total hip region (p < 0.05). Sex did not seem to affect BMD. In all three regions, a decrease in BMD with increasing duration since the onset of RA symptoms was observed. Disease severity, measured using the DAS28-ESR score, did not decrease BMD. There was an increase in functional disability, calculated using the HAQ score, with a decrease in BMD at all sites. RF positivity was associated with decreased BMD at the neck of the femur and total hip region but not the total lumbar spine. Long-term use of steroids (≥30 days) decreased BMD at all three sites. CONCLUSION: Our study reiterates the effect of RA on the BMD of patients. Advanced age, duration since symptom onset, physical disability, RF positivity, and long-term corticosteroid use are disease-related factors affecting BMD in patients with RA.

Increased Rheumatoid Factor production in patients with severe COVID-19.

BACKGROUND: Searching for Rheumatoid Factors (RF) in patients with coronavirus disease (COVID-19) has rarely been described. OBJECTIVES: To investigate the association between RF isotypes (IgM, IgA, and IgG) and different clinical presentations of COVID-19 in a series of Tunisian patients. STUDY DESIGN: Eighty-two COVID-19 patients were enrolled in this study. Symptomatic cases were recruited from the Department of COVID-19 and the intensive care unit (ICU) of the University Hospital of Mahdia, Tunisia, from January 2021 to March 2021. Different RF isotypes were assessed using a commercial enzyme-linked immunosorbent assay (ELISA). RESULTS: Forty-one patients (50%) had RF of any isotype. Thirty-two patients (39%) were tested positive for RF-IgM. Symptomatic forms of the disease were associated with RF-IgM positivity (p = 0.005). The mean concentration of RF-IgM was higher in the severe form than in the moderate and asymptomatic forms (p = 0.006). CONCLUSIONS: Our study suggests that the production of RF-IgM isotype is increased in patients with severe COVID-19.

Immune Checkpoint Inhibitor-Associated Remitting Seronegative Symmetrical Synovitis With Pitting Edema: Description of a New Entity by CanRIO.

OBJECTIVE: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is characterized by symmetrical synovitis with pitting edema and negative rheumatoid factor (RF). It has been described in a setting of malignancy, suggesting a paraneoplastic association. With the increasing use of immune checkpoint inhibitors (ICIs) for the treatment of cancers and emergence of immune-related adverse events (irAEs), our objective was to identify and describe cases of ICI-associated RS3PE (ICI-RS3PE) and compare them to non-ICI-RS3PE. METHODS: The Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) network is a collaboration of Canadian rheumatologists with experience in the management of patients with rheumatic irAEs (Rh-irAEs). Standardized data on adult patients with Rh-irAE have been collected as part of retrospective and prospective cohorts. In this study, detailed information on all cases of ICI-RS3PE from both cohorts were extracted and analyzed. RESULTS: We identified 11 cases of ICI-RS3PE. The most frequently observed malignancy was nonsmall cell lung cancer (4 of 11), followed by malignant melanoma (2 of 11) and cutaneous squamous cell carcinoma (2 of 11). The median time to onset of ICI-RS3PE was 26 weeks from ICI start and 52 weeks from diagnosis of malignancy. Seven patients had stable cancer prior to onset of ICI-RS3PE, 3 had partial response, and 1 had complete response. All patients received glucocorticoids. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) were needed in 10 patients. CONCLUSION: ICI-RS3PE may be an independent Rh-irAE, separate from paraneoplastic RS3PE. The symptoms of ICI-RS3PE responded well to glucocorticoids, but concomitant treatment with csDMARDs may be necessary.

Myocardial T1 mapping by cardiac magnetic resonance imaging shows early myocardial changes in treatment-naive patients with active rheumatoid arthritis and positive autoantibodies.

OBJECTIVES: We aimed to study whether myocardial changes are already detectable by cardiac magnetic resonance (CMR) imaging at the time of rheumatoid arthritis (RA) diagnosis. METHODS: This single-centre prospective study included 39 treatment-naive patients with early rheumatoid arthritis (ERA, symptom duration <1 year) without any history of heart disease, and 38 age- and sex-matched healthy volunteers. The disease severity was assessed with clinical evaluation (Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) score) and serological testing (rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA)). The ERA patients were classified into group A (DAS28-CRP score ≥3.2, positive RF and ACPA; n=17) and group B (not fulfilling the group A criteria). The ERA patients and healthy controls underwent 1.5T CMR. RESULTS: Group A patients had significantly higher myocardial global T1 relaxation times than the healthy controls, 987 [965, 1003] ms vs. 979 [960, 991] ms (median [IQR]; p=0.041). A significant difference in T1 was found in the basal, mid inferior and mid anterolateral segments. In a multivariate analysis, prolonged global T1 relaxation time was independently associated with female sex (95% CI [5.62, 51.31] ms, p=0.016), and group A status (95% CI [4.65, 39.01] ms p=0.014). CONCLUSIONS: At the time of diagnosis, ERA patients with a higher disease activity (DAS28-CRP score ≥3.2) and both positive RF and ACPA showed prolonged T1 relaxation times in basal myocardial segments. These segments could be most susceptible to the development of myocardial fibrosis, and a segmental reporting style could be useful when estimating the first signs of myocardial fibrosis.

Hypothyroidism and autoimmune thyroid disorders in rheumatoid arthritis: relationship with disease activity.

Background and aims: Thyroid function abnormalities and thyroid autoantibodies have previously been described in rheumatoid arthirits (RA) with limited data. In some studies, a relationship was found between thyroid autoantibodies and RA disease activity. However, there are not strong studies in the literature indicating the relationship between thyroid diseases and RA. The aim of this study was to determine the frequency of hypothyroidism and to investigate the relationship between thyroid hormone levels, autoantibodies and disease activity in patients with rheumatoid arthritis (RA). Methods : 1017 patients with the diagnosis of RA were recruited. This observational study was conducted between January 2014 and July 2015. Demographic variables were recorded. Anti-nuclear antibodies (ANA), anti-cyclic citrulli-nated peptide antibody (anti-CCP), Rheumatoid Factor (RF), C reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), anti-microsomal antibody (anti-TPO )and anti-thyroglobulin antibody (anti-TG) were determined. Visual analog score and Disease Activiy Score 28 (DAS-28) ESR and DAS-28 CRP were recorded. The relationship between thyroid hormone levels and thyroid antibodies and disease activity parameters were determined. Results: 98 (%9,7) patients had hypothyroidism and 61 (%6) patients had hyperthyroidism. 210 (20,7%) patients with RA was positive for TPOAb and 165(16,3%) for anti-TG. Positive correlation was detected between anti-TPO positivity and anti-CCP levels (p:0.005, r:0,274). In anti-TG antibody positive patients, there was a significant positive correlation of thyroid hormone levels with CRP and DAS 28-CRP (p:0.01, r:0,120; p:0.01, r:0,169). Conclusion: Thyroid autoantibodies were found to be positive in 16-21% of patients with RA. Though hypothyroidism is not very frequent in RA patients, autoimmune thyroid disease is quite common, which may be related to disease activity.

Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The International League of Associations for Rheumatology (ILAR) has defined JIA as "arthritis of unknown etiology persisting for ≥6 wk with an onset at <16 y of age, after excluding other causes of joint inflammation". Synovial inflammation is the result of a complex interplay of aberrant immune systems (both adaptive and innate) in a genetically susceptible individual, with possible external stimuli/triggers. Diagnosis of JIA essentially remains clinical, and laboratory investigations usually help to assess the severity of disease activity. Few investigations like antinuclear antibodies (ANA), human leukocyte antigen (HLA)-B27, and rheumatoid factor (RF) help to categorize or prognosticate a child with JIA. Timely use of effective therapeutic interventions including biological has shown good long-term outcomes of JIA.

Elevated serum soluble CD27 levels are associated with both disease activity and humoral immune activity in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the serum level of soluble CD27 (sCD27) and its potential clinical significance in rheumatoid arthritis (RA). METHODS: Serum sCD27 levels in RA patients, idiopathic inflammatory myopathy (IIM) patients, systemic lupus erythematosus (SLE) patients and healthy controls (HCs) were detected by enzyme-linked immunosorbent assay. The medical information and laboratory data of the patients were collected. Serum sCD27 levels in RA patients with different clinical features were analysed, as was the correlation between the clinical data and serum sCD27 levels. Independent samples t test, the Mann-Whitney U-test or Wilcoxon signed-rank test, and Spearman correlation were used for statistical analysis. RESULTS: Levels of sCD27 were elevated in RA patients (3898 [2525, 5834] pg/mL) compared with IIM patients (2467 [1939, 3324] pg/mL) or HCs (1659 ± 648 pg/mL) (p 0.001). In addition, serum sCD27 levels correlated with age, erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A, immunoglobulin G, complement 4 and disease activity score in 28 joints in RA patients. Levels of sCD27 were higher in RF-positive RA patients (6054 ± 5842 pg/mL) than in RF-negative patients (3902 ± 2098 pg/mL), and a similar finding was also observed in anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (5810 ± 5671 pg/mL) and anti-CCP-negative (4183 ± 2187 pg/mL) RA patients. Serum ESR, RF, IgA, IgG levels and DAS28-CRP were elevated in RA patients with higher sCD27 levels than in those with lower sCD27 levels (p<0.01). CONCLUSIONS: Serum sCD27 might be a promising biomarker that reflects both disease activity and humoral immunity activity in RA.

Influence of rheumatoid factor on serum drug levels of TNF inhibitors with different structures in rheumatoid arthritis.

OBJECTIVES: Certolizumab pegol (CZP), an Fc-free antibody fragment, has shown stable serum levels and steady efficacy in the treatment of RA patients, irrespective of RF levels at baseline. Here, we examine, in clinical practice, the effect of baseline RF and ACPA levels on serum drug levels of IFX, ADL and CZP an Fc-free antibody fragment. METHODS: This is a retrospective study performed in real-world patients. We assessed 170 patients with RA: 90 (53%) received IFX, 48 (28%) ADL and 32 (19%) CZP. Demographic and clinical variables, RF and ACPA levels were obtained at the baseline visit (T0), and patients were stratified based on negative, low, medium, or high levels. After 6 months (T6) serum drug levels and anti-drug antibodies (ADAb), were computed. RESULTS: While CZP serum levels did not differ across RF groups at T6, high baseline RF was linked to lower serum drug levels compared to RF negative status in treatment with complete monoclonal antibodies IFX and ADL. No differences in disease activity measured by DAS28 at baseline were observed across RF quartiles in patients treated with IFX or ADL. ADAb was observed in 26 patients with IFX, 3 with ADL and 1 with CZP, following 6 months of treatment. Patients with high baseline RF levels dropped out more frequently by secondary non-response in IFX or ADL than CZP (80% vs. 75% vs. 33%, p=0.002). CONCLUSIONS: In this real word data evaluation, CZP serum levels were independent of RF levels in patients however patients with high baseline RF levels who obtained IFX or ADL had lower serum drug levels at 6 months than baseline RF-negative patients. In addition, secondary non-response was more frequent in patients with high RF levels treated with IFX and ADL.

Serological and Molecular Characterization of Hepatitis C Virus-Related Cryoglobulinemic Vasculitis in Patients without Cryoprecipitate.

Prolonged B cells stimulation due to the Hepatitis C virus (HCV) can result in autoimmunity, stigmatized by rising levels of cryoglobulins (CGs), the rheumatoid factor (RF), and free light chains (FLC) of immunoglobulins (Ig) associated with a range of symptoms, from their absence to severe cryoglobulinemic vasculitis and lymphoma. Here, we aimed to identify an immunological signature for the earliest stages of vasculitis when cryoprecipitate is still not detectable. We firstly analyzed the IgG subclasses, FLC, and RF in 120 HCV-RNA-positive patients divided into four groups according to the type of cryoprecipitate and symptoms: 30 asymptomatic without cryoprecipitate (No Cryo), 30 with vasculitis symptoms but without CGs that we supposed were circulating but still not detectable (Circulating), 30 type II and 30 type III mixed cryoglobulinemia (Cryo II and Cryo III, respectively). Our results revealed that patients with supposed circulating CGs displayed a pattern of serological parameters that closely resembled Cryo II and Cryo III, with a stronger similarity to Cryo II. Accordingly, we analyzed the groups of Circulating and Cryo II for their immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements, finding a similar mixed distribution of monoclonal, oligoclonal, and polyclonal responses compared to a control group of ten HCV-RNA-negative patients recovered from infection, who displayed a 100% polyclonal response. Our results strengthened the hypothesis that circulating CGs are the origin of symptoms in HCV-RNA-positive patients without cryoprecipitate and demonstrated that an analysis of clonal IGH and TCR rearrangements is the best option for the early diagnosis of extrahepatic complications.

ASSOCIATION OF SOME IMMUNOLOGICAL BIOMARKERS WITH RHEUMATOID ARTHRITIS PATIENTS IN THI-QAR PROVINCE.

OBJECTIVE: The aim: The aim of this research is to evaluate some immunological biomarkers in cases of Rheumatoid arthritis and to verify their correlation with activity of disease among the population of Thi-Qar province. PATIENTS AND METHODS: Matherials and methods: This study included 45 cases of rheumatoid arthritis and 45 healthy subjects. All cases underwent complete history taking, thor¬ough clinical examination, and laboratory tests including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Anti-citrulline antibody (Anti-CCP) and rheumatoid factor (RF). IL-17and TNF-α blood level was measured by Enzyme Linked Immunosorbent Assay (ELISA) method. DAS-28 (Disease activity score 28) was evaluated. RESULTS: Results: Serum levels TNF-α was higher in Rheumatoid arthritis patients (424.3±19.46 pg/ml) than in healthy individuals (112.7±4.73 pg/ml), and IL-17 blood levels were higher in Rheumatoid arthritis patients (233.5±241.4 pg/ml) than the healthy individuals group (47.24±49.7 pg/ml). There was significant association found among IL-17, DAS-28, CRP and hemoglobin levels. CONCLUSION: Conclusions: In conclusion, IL-17 blood levels were significantly increased in peoples with rheumatoid arthritis than in healthy individuals. Its significant relationship with DAS-28 suggested that the level of IL-17 in serum could be important immunological biomarker for activity of disease in disease of Rheumatoid arthritis.

Correlation of serum citrullinated histone H3 levels with disease activity in patients with rheumatoid arthritis.

OBJECTIVES: Serum citrullinated histone H3 (CitH3) levels in humans with rheumatoid arthritis (RA) were examined and the associations between CitH3 levels and disease variables were investigated. METHODS: Serum CitH3 levels were measured using an enzyme-linked immunosorbent assay in 151 RA patients (69 with highly, 32 with moderately, and 20 with mildly active RA and 30 with RA in remission) and 56 healthy controls. Receiver operating characteristic curve analysis was performed to evaluate the discriminant capacity of CitH3 between highly/moderately active RA and RA in remission/mild activity. Furthermore, machine-learning methods were applied to construct a predictive model. RESULTS: CitH3 concentration was more upregulated in patients with highly and moderately active RA than in those with mild activity and remission. The area under the curve for CitH3 was 0.825 for discriminating between highly and mildly active RA, 0.840 for discriminating between highly active RA and RA in remission, 0.789 for discriminating between moderately and mildly active RA, and 0.829 for discriminating between moderately active RA and RA in remission. The correlation analysis revealed that serum CitH3 levels were positively associated with Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR), ESR, C-reactive protein, rheumatoid factor, and some routine blood parameters (WBC, RDW, PLT, N, and N%), while negatively associated with haemoglobin, lymphocyte percentage, and thyroid-stimulating hormone. Through machine learning, the optimal predictive model was selected and had high performance. CONCLUSIONS: CitH3 is significantly associated with disease activity and could serve as a useful candidate biomarker to assess disease activity in patients with RA.