Clinical implications of seropositive and seronegative autoantibody status in rheumatoid arthritis patients: A comparative multicentre observational study.

Background and Objectives: Rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP) have been used to improve the diagnosis and prognosis of rheumatoid arthritis (RA). However, their association with RA disease phenotypes, individually and in combination, is not well studied. The aim of the study was to compare patients' and disease characteristics, activity and severity in double seronegative (DNRA), single seropositive RF, single seropositive anti-CCP and double seropositive (DPRA) patients. Methods: Adults subjects with RA from Egyptian College of Rheumatology (ECR) database who had RF and anti-CCP results available were included. Demographic, clinical features, disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ) and laboratory data were collected and compared among different RA groups. Results: 5268 RA patients with mean age of 44.9±11.6 years, and 4477 (85%) were females. 2900 (55%) had DPRA, 892 (16.9%) had single positive RF, 597 (11.3%) had single positive anti-CCP while 879 (16.7%) had DNRA. Patients with DPRA had significantly high percentage of metabolic syndrome (19.3%, P < 0.001), and functional impairment using HAQ (P = 0.01). Older age (RRR [relative risk ratio]: 1.03, 95%CI: 1.0, 1.0, P = 0.029), greater DAS28 (RRR: 1.51, 95%CI: 1.2, 1.9, P < 0.001), higher steroid use (RRR: 2.4, 95%CI: 1.36, 4.25, P = 0.002) were at higher risk of DPRA while longer disease duration (RRR: 1.08, 95%CI: 1.01, 1.16, P = 0.017) and fibromyalgia syndrome (RRR: 2.54, 95%CI: 1.10, 5.88, P = 0.028) were associated with higher odds of single positive RF status. Conclusion: Dual antibody-positive status has higher disease activity and severity, and higher chance of development of metabolic syndrome; highlighting the implicated role of inflammation, atherogenesis and cardiovascular disease risk in RA.

Clinical, Immunological and Inflammatory Characteristics among Mexican Children with Different Subtypes of Juvenile Idiopathic Arthritis: Exploring the Correlation between Anti-Cyclic Citrullinated Peptide (anti-CCP) and Rheumatoid Factor (RF).

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood, affecting one to four of every 1000 children worldwide. It is characterized by joint inflammation lasting more than six weeks in children under 16 years. The aim of this study was to estimate the frequency of JIA subtypes in the Mexican patient population; compare clinical, immunological and inflammation markers by JIA subtype; and examine the correlation between these variables. METHODS: We conducted a cross-sectional study of 50 patients with JIA (2-15 years). We estimated the frequency of each JIA subtype, assessed and compared the immunological characteristics (RF, ANA and anti-CCP) by JIA subtype at the time of diagnosis using Kruskal-Wallis or chi-square tests, and calculated Spearman correlation coefficients between the assessments. RESULTS: Our analysis included 50 patients, 29 (58%) girls and 21 (42%) boys, aged at the time of diagnosis 10.56 ± 3.99 years. The frequencies of JIA subtypes were RF-seropositive polyarthritis (34%), RF-seronegative polyarthritis (28%), systemic arthritis (16%), oligoarthritis (14%) and arthritis-related enthesitis (8%). We found a significant association between sex and JIA subtype (p = 0.014). There was a significant difference in anti-CCP levels by JIA subtype (p < 0.001). We also detected positive correlations between RF and anti-CCP (r = 0.63, p < 0.001) and between age and anti-CCP (r = 0.29, p = 0.041). CONCLUSIONS: Our study suggests that the frequency of the polyarticular subtypes of JIA is higher in Mexican children compared to other populations. Our findings highlight the importance of considering the presence of anti-CCP and RF as important criteria when deciding on treatment for JIA patients as elevated levels of these antibodies may indicate early forms of adult rheumatoid arthritis.

Stroke risk in rheumatoid arthritis patients: exploring connections and implications for patient care.

Rheumatoid arthritis (RA) can independently increase the risk of stroke, affecting both young and adult RA patients. Recent attention has been drawn to the association between stroke and RA, supported by mounting evidence. Given that stroke is a significant and an urgent public health concern, this review aims to highlight the relationship between stroke and RA, covering mechanisms, underlying risk factors, early detection tools, and treatment implications. By uncovering the connection that links RA to stroke, we can pave the way for targeted healthcare practices and the development of preventive strategies for individuals with RA. Therefore, further research is imperative to deepen our understanding of this association and, ideally, guide treatment decisions for individuals at risk of both RA and stroke.

Serum calprotectin correlates more strongly with inflammation and disease activity in ACPA positive than ACPA negative rheumatoid arthritis.

OBJECTIVES: The aim of the present study was to evaluate performance of serum and synovial fluid levels of the granulocyte protein calprotectin as inflammatory biomarker in rheumatoid arthritis (RA) patients with knee synovitis. METHODS: 76 RA patients with ongoing knee synovitis were included. Data on disease activity score with 28 joints and their subcomponents and radiological destruction of the affected knee were collected. White blood cell count, C-reactive protein, anti-citrullinated peptide antibodies (ACPA) against cyclic citrullinated peptide version 2 (anti-CCP2), IgM rheumatoid factor (RF) and calprotectin were analysed in parallel in circulation and in synovial fluid (SF). Counts of polynuclear and mononuclear cells were measured in SF. RESULTS: Serum (S) calprotectin correlated stronger than SF-calprotectin with inflammatory markers and disease activity. Instead, SF-calprotectin showed a strong correlation to SF counts of white blood cells, and especially to polymorphonuclear cell counts (Spearman's rho = 0.72, p< 0.001). S-calprotectin showed markedly stronger correlation with inflammatory markers and disease activity in ACPA positive as compared with ACPA negative RA patients; a similar difference was observed for patients with and without IgM RF. CONCLUSION: The particularly strong association between circulating calprotectin and inflammation in ACPA positive RA is a new argument for a specific role for polymorphonuclear granulocytes/neutrophils in this RA subset. Measurement of calprotectin in SF does not convey any additional benefit compared with measurement in the circulation in RA patients with knee synovitis.

A study of the roles of some immunological biomarkers in the diagnosis of rheumatoid arthritis.

Autoimmune rheumatoid arthritis (RA) is a systemic condition closely correlated with a variety of autoantibodies (Abs) that could be considered diagnostic and prognostic markers. The current research was designed to detect the diagnostic values for a number (n) of these auto-Abs in RA detection and to evaluate the accuracy of a combined diagnostic scheme. This prospective study was conducted between September 2021 and August 2022 and included 110 subjects with RA, 70 individuals with other autoimmune disorders as positive controls (PC), and 50 unrelated, apparently healthy individuals as healthy controls (HC). The eligibility criteria for all study groups were followed stringently. An enzyme-linked immunosorbent assay (ELISA) was employed to measure rheumatoid factors (RF), cyclic citrullinated peptide antibodies (CCP-Abs), mutated citrullinated vimentin antibodies (MCV-Abs), anti-perinuclear factor antibodies (APF-Abs), and anti-keratin antibodies (AKA). We calculated the specificity, sensitivity, and predictive values of all auto-Abs. Significantly higher levels of anti-CCP-Abs, anti-MCV-Abs, APF-Abs, and AKAs were reported in the RA patients compared to the HC and PC subjects. RF levels, however, were only statistically elevated when compared to the HC individuals. Anti-APF-Abs had a higher sensitivity rate (70.9%), and anti-CCP-Abs had a higher specificity rate (94.16%) compared to other auto-Abs, whereas the combined detection scheme revealed a higher sensitivity (81.81%) and excellent specificity (90.83%) compared to the two former auto-Abs. Anti-perinuclear factor-Ab was a highly sensitive test, and CCP-Ab was a surpassingly specific assay for identifying RA. Furthermore, the combined detection scheme is an essential serological approach for RA diagnosis and crucial in differentiating this disease from other autoimmune diseases, thus promoting early diagnosis and treatment.

Periodontal health status, Porphyromonas gingivalis and anti-cyclic citrullinated peptide antibodies among rheumatoid arthritis patients.

Porphyromonas gingivalis (P. gingivalis) is the primary periodontal pathogen involved in protein citrullination, which triggers the production of anti-cyclic citrullinated peptide (anti-CCP) antibodies, exacerbating rheumatoid arthritis (RA). This study aims to evaluate the amount of P. gingivalis and its association with anti-CCP antibodies in RA patients with periodontitis. This cross-sectional study involves 100 RA patients with a mean age of 52.36 (SD 13.90) years. Smokers and patients with other uncontrolled systemic diseases were excluded. Disease Activity Score-28 (DAS-28) was used to determine RA disease severity. Periodontal parameters were examined to determine periodontal status. Subsequently, plaque samples were collected from the subgingival periodontal pocket for assessment of P. gingivalis bacterial load using the loop-mediated isothermal amplification method. Blood samples (5 ml) were obtained from all participants to analyse anti-CCP antibody levels. Data was analysed by using SPSS version 24.0. Most participants were female (85.0%) and had low RA disease severity (62%). The mean RA disease duration was 7.77 (SD 6.3) years, with a mean DAS-28 of 3.17 (SD 1.0). Forty-seven per cent of participants had periodontitis, but all periodontal parameters were not associated with RA disease activity (P = 0.38). P. gingivalis bacterial load ranged from 10 to 109 copies/µl. Fifty-five per cent of the collected samples showed positive anti-CCP antibody levels, but no significant association was observed with the P. gingivalis bacterial load (P = 0.58). Considering the study's limitations, although periodontitis is prevalent among RA patients, there is a lack of association between P. gingivalis bacterial load and anti-CCP antibody levels, which should be investigated further.

Effects of Human Leukocyte Antigen DRB1 Genetic Polymorphism on Anti-Cyclic Citrullinated Peptide (ANTI-CCP) and Rheumatoid Factor (RF) Expression in Rheumatoid Arthritis (RA) Patients.

Rheumatoid arthritis (RA) is a systemic disease characterized by non-infectious inflammation of the joints and surrounding tissues, which can cause severe health problems, affect the patient's daily life, and even cause death. RA can be clinically diagnosed by the occurrence of blood serological markers, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP). However, about 20% of RA patients exhibit negative results for both markers, which makes RA diagnosis difficult and, therefore, may delay the effective treatment. Previous studies found some evidence that human leukocyte antigen (HLA)-related genes might be the susceptibility genes for RA and their polymorphisms might contribute to varieties of susceptibility and disease severity. This study aimed for the genetic polymorphisms of the RA patient genome and their effects on the RA patient's serological makers, RF and anti-CCP. A total of 4580 patients' electronic medical records from 1992 to 2020 were retrieved from the China Medical University Hospital database. The most representative single-nucleotide polymorphisms (SNPs) were identified through a genome-wide association study (GWAS) followed by enzyme-linked immunosorbent assay (ELISA) validation using the blood from 30 additional RA patients. The results showed significant changes at the position of chromosome 6 with rs9270481 being the most significant locus, which indicated the location of the HLA-DRB1 gene. Further, patients with the CC genotype at this locus were more likely to exhibit negative results for RF and anti-CCP than those with the TT genotype. The C allele was also more likely to be associated with negative results for RF and anti-CCP. The results demonstrated that a genetic polymorphism at rs9270481 affected the expression of RF and anti-CCP in RA patients, which might indicate the necessity to develop a personalized treatment plan for each individual patient based on the genetic profile.

A Rare Case of Allergic Bronchopulmonary Aspergillosis Progressing to Cardiac Tamponade in the Al Qassim Region of Saudi Arabia.

Allergic bronchopulmonary aspergillosis (ABPA) is a condition characterized by an exaggerated response of the immune system (a hypersensitivity response) to the fungus Aspergillus. Aspergillus-associated pericarditis leading to pericardial tamponade is rare. In our case, we presented a case of a 22-year-old female asthmatic patient with no other medical conditions who presented to the emergency department (ED) complaining of severe chest tightness and shortness of breath. Echocardiography revealed significant pleural and pericardial effusion consistent with cardiac tamponade. Both pleural and pericardial fluids were hemorrhagic. Four months later, she presented to the ED with chief complaints of shortness of breath and a cough lasting two days. She was admitted as a case of asthma exacerbation. In the following months, when the patient visited the pulmonology outpatient clinic, the doctors recommended for specific IgE test. Allergen-specific IgE testing was positive for A. fumigatus to confirm the presence of ABPA. As we rolled out other causes of cardiac tamponade, we link the development of cardiac tamponade secondary to an underlying Aspergillus infection. We report this case with the aim of improving clinical knowledge regarding probable causes of cardiac tamponade in patients with asthma, which may facilitate the establishment of early diagnosis and treatment protocols.

Serological markers of rheumatoid arthritis in patients with primary biliary cholangitis and the vice versa: A Tunisian study.

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune disease of the liver characterized by destructive lymphocytic cholangitis and anti-mitochondrial antibodies (AMA). Anti-gp210 and anti-Sp100, are used for the diagnosis of PBC in AMA-negative PBC patients. Patients with PBC have a propensity to have an extrahepatic manifestation which is especially autoimmune. OBJECTIVE: We aimed to determine the frequency of serological markers of rheumatoid arthritis (RA) (CCP-Ab or RF) in PBC patients and to do the vice versa. METHODS: Our PBC study included 70 patients with PBC and 80 healthy blood donors (HBD) and our RA study included 75 patients with RA and 75 HBD. Anti-cyclic citrullinated peptide antibodies (CCP-Ab) and rheumatoid factor (RF) were performed by indirect ELISA. AMA, anti-Sp100 and anti-gp210 were determined by indirect immunofluorescence. RESULTS: RA autoantibodies (CCP-Ab or RF) were more frequent in PBC patients than in HBD (65.7% vs. 8.7% p ã€ˆ10-6). CCP-Ab were significantly more frequent in patients than in controls (15.7% vs. 2.5%; p = 0.004). Nine patients had both CCP-Ab and RF vs. none of controls (12.8% vs. 0%; p = 0.001). RF were detected in 45 patients with PBC and in 5 HBD (64.3% vs. 6.2%; p ã€ˆ10-6). In PBC patients, RF were more frequent than CCP-Ab (64.3% vs. 15.7%; p ã€ˆ10-6). RF-IgG were present in 18.5% of patients; RF-immunoglobulin (Ig) A in 34.3% and RF-IgM in 54.3%. These frequencies were significantly higher than those found in control group (1.2% for RF-IgG (p ã€ˆ10-3); 0% for RF-IgA (p ã€ˆ10-6); and 6.2% for RF-IgM (p ã€ˆ10-6)). In our PBC patients, RF-IgA were more frequent than RF-IgG (34.3% vs. 18.5%; p = 0.03) and than CCP-Ab (34.3% vs. 15.7%; p = 0.01). Six patients had only RF-IgA versus none of the control group (8.6% vs. 0%; p = 0.01). AMA, anti-Sp100 and anti-gp 210 were absent in all RA patients. CONCLUSIONS: Serological markers of RA were more frequent in PBC patients than in HBD and the vice versa was not true.

Angiomatous meningioma associated with rapidly aggravated peritumoral leptomeningitis: A case report.

Background: A special type of meningioma is known to have infiltrated inflammatory cells within the tumor, associated with peritumoral inflammation. However, there have been no reports of meningioma with inflammatory response only around the tumor, without inflammatory cells within the tumor itself. Case Description: A 70-year-old woman presented with transient right hemiparesis due to an extra-axial tumor on the left frontal convexity. The tumor appeared hypointense on T1-weighted magnetic resonance images and hyperintense on T2-weighted images without peritumoral edema, and was homogenously enhanced associated with the peritumoral leptomeningeal enhancement. Cerebrospinal fluid examination showed an increase in the number of inflammatory cells with a predominance of mononuclear cells. During the following 1 month, the tumor size was unchanged, but the peritumoral leptomeningeal enhancement was remarkably enlarged with uncontrolled focal seizures. The tumor was subtotally removed and semisolid substances in the subarachnoid space were biopsied. Pathological examination with immunostaining revealed angiomatous meningioma: the tumor had no inflammatory cell infiltration within it, but was associated with the infiltration of immunoglobulin G4-negative lymphocytes into the border zone between the tumor and the dura mater, as well as numerous neutrophils and fibrinous exudates in the peritumoral subarachnoid space. The tumor removal rapidly improved the leptomeningeal enhancement and inflammatory reactions. Conclusion: The authors reported the first case of angiomatous meningioma associated with massive peritumoral inflammation without inflammatory infiltrates within the tumor itself.

Dual rheumatoid factor and anti-cyclic citrullinated peptide antibody positivity affects the manifestations of rheumatoid arthritis.

Introduction: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically. Methods: We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative. We compared the demographics, Disease Activity Score-28, Health Assessment Questionnaire score, quality of life using Short Form 36 and the use of prednisolone and disease-modifying antirheumatic drugs (DMARDs) of these patient groups. Results: Four hundred and ninety-one patients (67.2%) were ACPA+RF+, 54 (7.4%) were ACPA+RF-, 82 (11.2%) were ACPA-RF+ and 104 (14.2%) were ACPA-RF-. Mean disease duration before the study entry was not different in the four groups. Patients with older age of onset were less likely to be positive for RF and ACPA. Fewer ACPA+RF+ patients were in remission compared to those in the other groups (P < 0.05). Erythrocyte sedimentation rate (ESR) was higher at study entry in the ACPA+RF+ group (40.4 mm/h vs. 30.6-30.9 mm/h, P < 0.05). Prednisolone and number of DMARDs used were higher in the ACPA+RF+ group compared to the doubly negative group. There were no differences in the functional status and quality of life. Conclusions: RA patients who were positive for both ACPA and RF had lower remission rate, higher baseline ESR and required more corticosteroid and DMARD treatment compared to those who were singly positive or doubly negative. Being doubly positive confers a worse outcome to RA patients.

Shared epitope classification methods according to Gregersen and de Vries allow adequate characterization of patients with rheumatoid arthritis in a Colombian population

Introduction: The most important genetic association in rheumatoid arthritis (RA) is presented with some alleles from the HLA-DRB1 gene that encode the shared epitope (SE). Objectives: To apply the SE classification methods of Gregersen, de Vries, Raychaudhuri, Mattey, and Tezenas du Montcel in a group of Colombian patients with RA and determine the most common HLA-DRB1 alleles in the population. Methods: RA diagnosis, genetic study of the HLA-DRB1 region using Luminex technology in 50 RA and 50 healthy subjects. For the classification analysis, Fisher's exact test and chi-squared test were applied. Tables were created to count the RA-related alleles. We used odds ratio to determine the risk between the presence of the shared epitope (SE) and anti-cyclic citrullinated peptides (Anti-CCP). Results: Gregersen and de Vries methods were suitable for the characterization of RA in this population (p = .006). The most prevalent HLA-DRB1 alleles in the RA group were 14:02,04:04, 08:02,04:05, and 10:01. High frequencies of the 07:01, 03:01,13:02,01:02, and 12:01 HLA-DRB1 alleles were found in the healthy population. HLA-DRB1 alleles with similar distribution in both populations were 04:07, 15:01, 11:01, 16:02, and 01:01. A high frequency of SE + was observed in Anti-CCP + individuals (63.15%); however, this was not statistically significant [OR2.4 (.63-9.01); p = .19]. Conclusion: The SE classification methods of Gregersen and de Vries were adequate in characterizing RA in a Colombian population group. An equivalence of 100% was verified between the susceptibility alleles defined by de Vries and the alleles assigned as SE according to Gregersen.

Introducción: La asociación genética más importante en artritis reumatoide (AR) se presenta con algunos alelos del gen HLA DRB1 que codifican el epítope compartido (EC). Objetivos: Aplicar los métodos de clasificación de EC de Gregersen et al., de Vries et al., Raychaudhuri et al., Mattey et al., y Tezenas du Montcel et al., en un grupo de pacientes colombianos con AR, y determinar los alelos HLA DRB1 más frecuentes en esta población. Métodos: Diagnóstico para AR, estudio genético de la región HLA DRB1 por tecnología Luminex® de 50 sujetos AR y 50 sanos. Para análisis comparativos de clasificaciones EC, se aplicaron las pruebas test exacto de Fisher y Chi-cuadrado y se realizaron tablas de conteos para los alelos relacionados con AR. Se estimó la razón de odds para determinar el riesgo entre la presencia de EC y los anticuerpos antipéptidos cíclicos citrulinados (anti-PCC). Resultados: Los métodos de Gregersen et al. y de Vries et al. fueron adecuados para la caracterización de AR en esta población (p = 0,006). Los alelos HLA DRB1 más prevalentes en el grupo AR fueron 14:02, 04:04, 08:02, 04:05 y 10:01. Se encontraron altas frecuencias de los alelos HLA DRB1 07:01, 03:01,13:02, 01:02 y 12:01 en población sana. Alelos HLA DRB1 con distribución similar en ambas poblaciones fueron: 04:07, 15:01, 11:01, 16:02 y 01:01. Se observó alta frecuencia de individuos EC+ en el grupo AR anti-PCC+ (63,15%); no obstante, sin asociación estadística (OR: 2,4 [0,63-9,01]; p = 0,19). Conclusión: Los métodos de clasificación para EC de Gregersen et al. y de Vries et al. fueron adecuados caracterizando AR en un grupo de población colombiana. Se corroboró equivalencia del 100% entre los alelos de susceptibilidad definidos por de Vries y los alelos asignados como EC según Gregersen et al.

Ultrasound tenosynovitis: A differential feature of patients with seronegative rheumatoid arthritis.

OBJECTIVE: To identify differential features between patients with seropositive and seronegative rheumatoid arthritis (RA). METHOD: Prospective cohort study, including patients who were admitted for polyarthralgia. At baseline was performed: laboratory studies, X-rays of hands and feet, ultrasound of both hands with power Doppler technique, clinical data and clinimetry. In subsequent visits the definitive diagnosis of RA was established or not. It was considered as seronegative RA when patients were negative for both RF and ACPAs. RESULTS: 746 patients were included, of which 128 (17.1%) ended with a final diagnosis of RA. Of these 128 patients, 87 (67.9%) were seropositive RA, while 41 (32%) were seronegative RA. The only feature that showed significant differences was the presence of tenosynovitis detected by ultrasound with a positive power Doppler signal, 13.7% of the patients with seropositive RA vs 41.6% of the patients with seronegative RA (p=0.0028). CONCLUSION: The only differential feature of patients with seronegative RA was the higher proportion of tenosynovitis detected by ultrasound.

Serum sirtuin-1 a potential marker in the diagnosis of rheumatoid arthritis.

Introduction: To explore the value of serum sirtuin-1 (SIRT1) in the diagnosis and evaluation of joint mobility of rheumatoid arthritis (RA). Materials and Methods: Serum was randomly obtained from 212 RA patients,210 non-RA patients and 58 healthy controls in a large tertiary first-class hospital in Jiangxi province from November 2021 to June 2022. The level of serum Sirt1,anti-cyclic citrulline polypeptide antibody (anti-CCP), anti-mutant citrulline vimentin antibody (anti-MCV), rheumatoid factor (RF),high-mobility group box 1 (HMGB1), collagen triple helix repeat containing 1 (CTHRC1), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were detected by ELISA, to explore the correlation between them and their value in the diagnosis and evaluation of joint range of motion of RA and statistically analyse their diagnostic efficiency. Results: ① The level of all markers was higher in the RA group than in the non-RA group and the healthy controls (p < 0.05). ② The AUC of the SIRT1 was 0.882, second only to the anti-MCV and anti-CCP. ③ The anti-CCP showed the highest sensitivity to RA diagnosis of 0.948. The specificity and positive predictive value of SIRT1 for the diagnosis of RA were the highest, which are 0.959 and 0.934 respectively. ④ In serial combination, SIRT1/anti-CCP、SIRT1/anti-MCV showed the highest specificity.SIRT1/anti-CCP in parallel combination had the highest sensitivity. ⑤ SIRT1 showed a significant correlation with other markers and DAS28 scores (p < 0.01). Conclusion: SIRT1 can be used as a new serological marker for RA diagnosis, which has a significant correlation with RA joint mobility and has a certain reference value in RA differential diagnosis, providing a new detection basis for RA differential diagnosis.

Ultrasound tenosynovitis: A differential feature of patients with seronegative rheumatoid arthritis / Tenosinovitis ecográfica: una característica diferencial de pacientes con artritis reumatoide seronegativa

Objective: To identify differential features between patients with seropositive and seronegative rheumatoid arthritis (RA). Method: Prospective cohort study, including patients who were admitted for polyarthralgia. At baseline was performed: laboratory studies, X-rays of hands and feet, ultrasound of both hands with power Doppler technique, clinical data and clinimetry. In subsequent visits the definitive diagnosis of RA was established or not. It was considered as seronegative RA when patients were negative for both RF and ACPAs. Results: 746 patients were included, of which 128 (17.1%) ended with a final diagnosis of RA. Of these 128 patients, 87 (67.9%) were seropositive RA, while 41 (32%) were seronegative RA. The only feature that showed significant differences was the presence of tenosynovitis detected by ultrasound with a positive power Doppler signal, 13.7% of the patients with seropositive RA vs 41.6% of the patients with seronegative RA (p=0.0028). Conclusion: The only differential feature of patients with seronegative RA was the higher proportion of tenosynovitis detected by ultrasound.(AU)

Objetivo: Identificar características diferenciales entre pacientes con artritis reumatoide (AR) seropositivos y seronegativos. Método: Estudio de cohorte prospectivo, incluyendo pacientes con poliartralgias. Al inicio se realizó: estudios de laboratorio, radiografías de manos y pies, ecografía de ambas manos con técnica power doppler, datos clínicos y clinimetría. En visitas posteriores se estableció o no el diagnóstico definitivo de AR. Se consideró AR seronegativa cuando los pacientes eran negativos tanto para factor reumatoide como para anticuerpos antipéptido cíclico citrulinado. Resultados: Se incluyeron 746 pacientes, de los cuales 128 (17,1%) terminaron con diagnóstico final de AR. De estos 128 pacientes, 87 (67,9%) eran AR seropositivos, mientras que 41 (32%) eran AR seronegativos.La única característica que mostró diferencias significativas fue la presencia de tenosinovitis detectada por ecografía con señal power doppler positiva, el 13,7% de los pacientes con AR seropositiva frente al 41,6% de los pacientes con AR seronegativa (p=0,0028). Conclusión: El único rasgo diferencial de los pacientes con AR seronegativa fue la mayor proporción de tenosinovitis detectadas por ecografía.(AU)

Association Between Rheumatic Autoantibodies and Immune-Related Adverse Events.

BACKGROUND: Side effects of immune checkpoint inhibitors (ICIs), called immune-related adverse events (irAEs), closely resemble primary autoimmune or rheumatic diseases. We aimed to understand the clinical utility of rheumatic autoantibodies (rhAbs) for diagnosing irAEs. PATIENTS AND METHODS: Patients without pre-existing autoimmune disease (pAID) who had cancer treated with ICI(s) treatment from 1/1/2011 to 12/21/2020 and a rhAb checked were retrospectively identified. Logistic regression assessed associations between autoantibodies and irAEs, cancer outcome, and survival. Specificity, sensitivity, and positive/negative predictive values (PPV, NPV) were estimated for key rhAbs and ICI-arthritis. Kaplan-Meier analyzed objective response rate (ORR) and overall survival (OS). RESULTS: A total of 2662 patients were treated with≥1 ICIs. One hundred and thirty-five without pAID had ≥ 1 rhAb tested. Of which 70/135(52%) were female; median age at cancer diagnosis was 62 years with most common cancers: melanoma (23%) or non-small cell lung cancer (21%), 96/135 (75%) were anti-PD1/PDL1 treated. Eighty had a rhAb ordered before ICI, 96 after ICI, and 12 before and after. Eighty-two (61%) experienced an irAE, 33 (24%) with rheumatic-irAE. Pre-ICI RF showed significant association with rheumatic-irAEs (OR = 25, 95% CI, 1.52-410.86, P = .024). Pre- and post-ICI RF yielded high specificity for ICI-arthritis (93% and 78%), as did pre- and post-ICI CCP (100% and 91%). Pre-ICI RF carried 93% NPV and pre-ICI CCP had 89% PPV for ICI-arthritis. No variables were significantly correlated with ORR. Any-type irAE, rheumatic-irAE and ICI-arthritis were all associated with better OS (P = .000, P = .028, P = .019). CONCLUSIONS: Pre-ICI RF was associated with higher odds of rheumatic-irAEs. IrAEs had better OS; therefore, clinical contextualization for rhAbs is critical to prevent unnecessary withholding of lifesaving ICI for fear of irAEs.

Association of Interleukin-10 Genotypes and Anticyclic Citrullinated Peptide Antibodies with Rheumatoid Arthritis.

Background: According to recent evidence, there is an association between some genetic factors and rheumatoid arthritis (RA). The aim of this study was to determine whether genetic variations in the interleukin 10 (IL10) and anti-cyclic citrullinated peptide (Anti-CCP) antibody loci were linked to RA. Methods: In this hospital-based case-control study with 224 cases and 194 healthy individuals, we investigated the association of IL-10 genotypes and anti-CCP antibodies with RA. Independent sample t, chi-square, and Fisher exact tests were used to assess the association between study variables. Results: Frequency of IL-10 -1082 A/G genotype in RA patients is significantly higher than the control group (odds ratio [OR], 1.67 [95% CI, 1.11-2.51]) (p=0.009), while the frequency of IL-10-1082 A/A and G/G polymorphisms in RA patients was lower than controls and this finding for G/G polymorphism was statistically significant (p=0.01). No significant difference was observed between the 2 studied groups regarding IL-10-592 C/C, C/A, and A/A polymorphisms (p>0.05). The chance of RA occurrence among persons with positive anti-CCP was significantly (63.3 times [22.7-176.5]) higher than individuals with negative anti-CCP (p<0.001). Conclusion: According to our data, the chance of anti-CCP positivity in persons who have IL-10 genotype 1082 A/G is higher. Further studies are recommended to determine the relationship between IL-10 genotype 1082 G/A and RA. If such a relationship is proven, this finding as a diagnostic clue can help rheumatologists in the early detection of RA.

Anti-Cyclic Citrullinated Peptide Antibody Index in the Cerebrospinal Fluid for the Diagnosis and Monitoring of Rheumatoid Meningitis.

Rheumatoid meningitis (RM) is a rare but often aggressive neurological complication of rheumatoid arthritis. The diagnosis of RM, besides the clinical, radiological, and laboratory criteria, usually requires a cerebral biopsy. Based on the two cases presented in this paper, we propose a new laboratory marker. Cerebrospinal fluid and serum anti-cyclic citrullinated peptide (CCP) IgG were measured, and the intrathecal synthesis of anti-CCP antibodies (anti-CCP antibody index) was calculated using the hyperbolic function. The anti-CCP antibody index was positive in both cases at first diagnosis and progressively decreased after treatments. Together with clinical and radiological criteria, the calculation of the anti-CCP intrathecal synthesis, more than the simple measurement of serum or cerebrospinal fluid anti-CCP antibody titers, may represent a useful tool for RM diagnosis and, possibly, for treatment response.

Comparison of different assays for the detection of anticyclic citrullinated peptide antibodies in patients with rheumatoid arthritis.

Objective: To evaluate a novel fully automated immunoturbidimetric assay developed by Qiangsheng Biotechnology Company for the detection of anticyclic citrullinated peptide antibodies (anti-CCP) in serum of patients with rheumatoid arthritis (RA) and compare it to the conventional EUROIMMUN- anti-CCP ELISA. Two other commonly used automated assays, the Elecsys anti-CCP assay, an ECLIA that is run on the Modular Analystics E170 (Cobas Diagnostics, Germany), and an anti-CCP CLIA developed by YHLO that is run on the iFlash 3000 Chemiluminescence Immunoassay Analyzer, were included as reference standards. Methods: A total of 264 serum samples were collected from patients attending the First People's Hospital of Wenling affiliated to Wenzhou Medical University between July 2020 and November 2020. These included 131 serum samples collected from patients with RA, 70 serum samples collected from patients with other autoimmune diseases, and 63 serum samples collected from healthy controls at a physical examination. The clinical performance and sensitivity and specificity of the four anti-CCP assays for the diagnosis of RA were compared using receiver operating characteristic (ROC) curve analysis. Results: The Kappa statistic indicated almost perfect agreement between the EUROIMMUN-anti-CCP ELISA and the Elecsys anti-CCP ECLIA (Cobas) (0.863), the EUROIMMUN-anti-CCP ELISA and the anti-CCP CLIA (YHLO) (0.862), and the Elecsys anti-CCP ECLIA (Cobas) and the anti-CCP CLIA (YHLO) (0.816). On ROC curve analysis, AUC values were 0.955 for the EUROIMMUN-anti-CCP ELISA, 0.948 for the anti-CCP CLIA (YHLO), 0.947 for the Elecsys anti-CCP ECLIA (Cobas) and 0.903 for Qiangsheng, indicating all the assays had a good diagnostic performance for RA. Conclusion: The anti-CCP assays provided similar diagnostic information. The novel fully automated immunoturbidimetric assay for anti-CCP developed by Qiangsheng Biotechnology Company may be especially useful for large scale clinical screening in RA as it has a shorter testing time than the commercially available alternatives.

Anti-Carbamylated Protein (Anti-CarP) Antibodies in Patients Evaluated for Suspected Rheumatoid Arthritis.

(1) Background: Anti-carbamylated protein (CarP) antibodies have been studied as novel markers to aid in the diagnosis and prognosis of rheumatoid arthritis. (2) Methods: A total of 265 samples were included in the evaluation, for which 98 had results for anti-cyclic citrullinated peptide (CCP), 86 for rheumatoid factor (RF), and 212 for 14-3-3 eta protein. Anti-CarP antibodies were measured using a fetal calf serum-based single-step assay (research use only, Inova Diagnostics, San Diego, CA). (3) Results: Anti-CarP antibodies were significantly higher and more frequent in anti-CCP3.1+ (p = 0.0025), RF+ (p = 0.0043) and 14-3-3 eta+ (p = 0.028) samples compared to the negative counterpart group. In addition, isolated anti-CarP positivity occurred in samples negative for anti-CCP3.1, RF, or 14-3-3 eta. When anti-CarP antibodies were compared to each of the RF, anti-CCP3.1, and 14-3-3 eta by receiver operating characteristic (ROC) analyses, the area under the curve (AUC) values of 0.71 (RF), 0.68 (anti-CCP3.1), and 0.59 (14-3-3 eta), respectively, demonstrated a moderate correlation. Using an UpSet plot, we determined that 10.6% of the samples with available results for anti-CCP3.1, RF, and anti-CarP showed triple positivity. (4) Conclusions: Anti-carbamylated protein (anti-CarP) antibodies can be detected in anti-CCP, RF and 14-3-3 eta-positive and -negative patients, potentially identifying specific subsets of patients.