Are the cut-offs of the rheumatoid factor and anti-cyclic citrullinated peptide antibody different to distinguish rheumatoid arthritis from their primary differential diagnoses?

OBJECTIVE: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP) are commonly used for diagnosis of rheumatoid arthritis (RA), although other rheumatic diseases with arthritis can test positive. This study aimed to determine the cutoff values for RF and anti-CCP with the best diagnostic performance in a sample of patients with RA, compared with other rheumatic diseases. METHODS: This was a descriptive, prospective study. EUROINMMUN enzyme-linked immunosorbent assays for RF isotypes immunoglobulin (Ig) A (IgA), IgG and IgM and third-generation assay IgG for anti-CCP were used in serum samples of patients with RA, other rheumatic diseases and healthy subjects. The cutoff with the best diagnostic performance was determined by the Youden Index and receiver operating characteristic analysis Results: Three hundred and thirty-two serum samples were analysed. The cutoffs proposed in our population were for RF in RA patients versus other rheumatic diseases, and healthy subjects IgM 135 IU/mL, for each disease, compared with RA, were psoriatic arthritis (Psa) IgA 47.2 IU/mL, clinically suspicious arthralgia (CSA) IgA 39.5 IU/mL, primary Sjögren's syndrome (pSS) IgM 180.6 IU/mL, systemic lupus erythematosus (SLE) IgA 42.6 IU/mL, primary fibromyalgia (pFM) IgM 68.6 IU/mL, osteoarthritis (OA) IgM 48 IU/mL, gout IgM 117 IU/mL and healthy IgM 16.3 IU/mL. For anti-CCP, in RA patients versus other rheumatic diseases, and healthy subjects 6.95 IU/mL, for each disease, compared with RA, were Psa 6.8 IU/mL, CSA 9.95 IU/mL, pSS 20.7 IU/mL, SLE 6 IU /mL, pFM 11.8 IU/mL, OA 11.9 IU/mL, gout 5 IU/mL and healthy 5 IU/mL. CONCLUSION: Irrespective of the manufacturer's suggested cutoff, the RA versus differential diagnosis cutoffs must be considered.

Patients with seronegative rheumatoid arthritis have a different phenotype than seropositive patients: A clinical and ultrasound study.

Introduction: Rheumatoid arthritis (RA) is an inflammatory disease whose clinical phenotype largely depends on the presence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Seronegative RA appears to be a less severe disease, but this remains controversial. This study aimed to assess whether seronegative patients show a less severe disease than seropositive patients. Methods: A cross-sectional study was conducted on RA outpatients from a single center. Clinical activity scales, laboratory evaluations, and cardiovascular risk scores were assessed. Musculoskeletal ultrasound (US) examinations were performed. Results: One hundred and fourteen patients were enrolled. Eighty-five were seropositive (76% women) and 29 seronegative (93% women). Seropositive patients had a younger age at disease onset (43 ± 14 vs. 54 ± 11; p = 0.001) and used sulfasalazine (47 vs. 17%; p = 0.004) and glucocorticoids (36 vs. 10%; p = 0.007) more frequently. No differences in clinical activity scales and in 10-year cardiovascular risk were observed. Pathological US data were found more frequently in seropositive patients in the 2nd metacarpophalangeal (MCP) joint, both in grayscale (71 vs. 38%; p = 0.008) and in power Doppler (PD; 53 vs. 9%; p < 0.001); erosions (36 vs. 9%; p = 0.020) were also more frequent. We found greater severity of PD signals in the 2nd MCP and 3rd MCP joints of the seropositive patients, while synovitis severity was higher only in the 2nd MCP joints. The percentage of total joints with erosions (9 vs. 1%; p < 0.001) and 2nd MCP joints with erosions (25 vs. 7%; p < 0.001) was higher in seropositive patients. Conclusion: RA patients show a differentiated phenotype according to their ACPA and RF status. In seronegative patients, RA begins later in life and has a lower requirement for antirheumatic therapies. On US evaluation, seropositive patients show more joint damage, especially in MCP joints. Despite this, long-term cardiovascular risk is similar among RA patients, regardless of their RF and ACPA status.

Anti-carbamylated protein antibodies positivity and disease activity in Hispanic patients with established rheumatoid arthritis: An observational study.

OBJECTIVES: We aimed to determine the prevalence of anti-carbamylated protein (anti-CarP) antibodies in Mexican Hispanics with established rheumatoid arthritis (RA) and to assess their relationship with disease activity. METHODS: A cohort study was conducted in 278 patients with established RA during an 18-month follow-up. We measured IgG/IgM/IgA rheumatoid factor (RF), IgG anticitrullinated protein antibodies (ACPA) and IgG/IgM/IgA anti-CarP antibodies using enzyme-linked immunosorbent assay (ELISA). For disease activity, we performed the 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR). Repeated measures one-way ANOVA was used to test the association between anti-CarP IgG antibody status and longitudinal DAS28-ESR scores. Patients were evaluated at baseline and at 6, 12, and 18 months during follow-up. RESULTS: Anti-CarP IgG antibodies were positive in 47.8% of patients and, accounting for all isotypes, in 9.5% of patients with negative RF and ACPA. Triple antibody positivity was present in 42.6% of patients in our sample. Anti-CarP IgG antibody positivity did not show statistically significant differences in mean DAS28-ESR when compared to anti-CarP IgG antibody negative patients at baseline, 6, 12 or 18 months. CONCLUSION: Anti-CarP IgG antibodies are not associated to a higher disease activity in Hispanic patients with established RA. Our findings suggest that the clinical value of measuring anti-CarP antibodies in RA diminishes over time.

Clinical and laboratory features of patients with undifferentiated spondyloarthritis and ankylosing spondylitis / Características clínicas y de laboratorio de pacientes con espondiloartritis indiferenciada y espondilitis anquilosante

ABSTRACT BACKGROUND: The terms Spondyloarthritis and spondyloarthropathy (Spa) are used to define a group of diseases with related clinical characteristics and genetics. AIM: To report the clinical and demographic characteristics of ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (USpA) and to evaluate the frequency of cyclic citrullinated peptide antibody (anti-CCP) positivity. MATERIAL AND METHODS: Two hundred patients with USpA or AS, 100 control patients with a diagnosis of rheumatoid arthritis (RA) and 100 healthy volunteers were included. For each patient, their detailed medical histories, physical examination, whole blood counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-CCP, routine biochemical tests, and HLA-B27 test results were evaluated. ASDAS and BASDAI scores and morning stiffness were used to evaluate the disease activity. RESULTS: The presenting symptom of 73 (73%) patients in the AS group and 58 (58%) patients in the USpA group was pain in axial joints. A family history of Spa was positive in 32 patients from both groups (32%). A positive HLA-B27 was found in 55% of the AS group and 25% of the USpA group (p < 0.01 for the difference between groups). The frequency of positive HLA-B27 was significantly higher in individuals with a family history of SpA (p = 0.022). A positive Anti-CCP was found in 56% of the RA group, a significantly higher frequency compared with other groups (p < 0.001). The frequency of positive Anti-CCP in patients in AS (9%) and USpA (6%) was significantly higher than in healthy controls (p < 0.001). CONCLUSIONS: The frequency of anti-CCP positivity was higher in SpA patients than in healthy controls.

INTRODUCCIÓN: Los términos espondiloartritis y espondiloatropatia (Spa) se usan para definir un grupo de enfermedades con características y genética relacionadas. OBJETIVO: Informar las características clínicas y demográficas de la espondilitis anquilosante (EA) y espondiloartritis indiferenciada (USpA) - y para evaluar la frecuencia de positividad del anticuerpo péptido citrulinado cíclico (anti-CCP). MATERIAL Y MÉTODOS: En este estudio observacional se incluyeron doscientos pacientes con USpA y EA, 100 pacientes control con diagnóstico de artritis reumatoide (AR) y 100 voluntarios sanos. Se evaluó la historia clínica, exámen físico, recuentos sanguíneos completos, velocidad de sedimentación globular (ESR), proteína C reactiva (PCR), anti-CCP, pruebas bioquímicas de rutina y resultados de la prueba HLA-B27. Para evaluar la actividad de la enfermedad se utilizaron las puntuaciones ASDAS y BASDAI y la rigidez matutina. RESULTADOS: El síntoma inicial de 73 (73%) pacientes en el grupo de EA y 58 (58%) pacientes en el grupo de USpA fue dolor en las articulaciones axiales. Treinta y dos pacientes de cada grupo (32%) tenían antecedentes familiares de SPA. HLA-B27 fue positivo en el 55% del grupo AS y el 25% del grupo USpA con una diferencia significativa entre los dos grupos (p < 0.001). La frecuencia de positividad HLA-B27 fue mayor en individuos con historia familiar de SpA (p = 0,02). Se encontraron anti-CCP positivos en el 56% del grupo con AR, una frecuencia significativamente mayor en comparación con otros grupos (p < 0,01). La frecuencia de anti-CCP positivo fue mayor los pacientes con AS (9%) y USpA (6%) que en el grupo sano (p < 0,001). CONCLUSIONES: La frecuencia de positividad anti-CCP fue mayor en los grupos de SpA en comparación con los grupos control sanos.

Effects of nonsurgical periodontal therapy in patients with rheumatoid arthritis: a prospective before and after study / Efectos de la terapia periodontal no quirúrgica en pacientes con artritis reumatoide: estudio prospectivo de antes y después

Abstract Background: periodontal therapy has been suggested to have systemic effects. However, studies of periodontal therapy in rheumatoid arthritis patients have produced controversial results. Aim: To compare the effects of nonsurgical periodontal therapy on biochemical markers of rheumatoid arthritis and periodontal parameters in patients with and without rheumatoid arthritis. Methods: a prospective before-and-after study was conducted that included 21 participants without and 29 participants with rheumatoid arthritis. Periodontal parameters, Porphyromonas gingivalis detection, C-reactive protein, rheumatoid factor and anti-citrullinated protein antibodies were measured at baseline and three months after nonsurgical periodontal therapy and the changes were statistically assessed. Results: In general, both groups presented statistically significant improvement in periodontal parameters (p<0.05). There was an increase in the counts of P. gingivalis in both groups at three months. In addition, there was a reduction in levels of anti-citrullinated protein antibodies and rheumatoid factor in participants with rheumatoid arthritis. In contrast, C-reactive protein levels increased in both groups but were higher in the rheumatoid arthritis group. Periodontal parameters in rheumatoid arthritis participants under disease-modifying antirheumatic drugs presented a slightly higher improvement (p <0.05). Conclusions: Nonsurgical periodontal therapy has similar improvements in periodontal parameters in patients with and without rheumatoid arthritis. In addition, nonsurgical periodontal therapy may benefit serum levels of anti-citrullinated protein antibodies and rheumatoid factors in patients with rheumatoid arthritis. NCT04658615.

Resumen Antecedentes: se ha sugerido que la terapia periodontal tiene efectos sistémicos. Sin embargo, los estudios de la terapia periodontal en pacientes con artritis reumatoide han producido resultados controvertidos. Objetivo: comparar los efectos de la terapia periodontal no quirúrgica sobre los marcadores bioquímicos de la artritis reumatoide y los parámetros periodontales en pacientes con y sin artritis reumatoide. Métodos: se realizó un estudio prospectivo de antes y después que incluyó a 21 participantes sin artritis reumatoide y 29 participantes con artritis reumatoide. Se midieron los parámetros periodontales, detección de Porphyromonas gingivalis, proteína C reactiva, factor reumatoide y anticuerpos anti-proteína citrulinada al inicio del estudio y tres meses después de la terapia periodontal no quirúrgica y los cambios se evaluaron estadísticamente. Resultados: En general, ambos grupos presentaron mejoría estadísticamente significativa en los parámetros periodontales (p <0.05). Hubo un aumento en los recuentos de P. gingivalis en ambos grupos a los tres meses. Además, hubo una reducción en los niveles de anticuerpos anti-proteína citrulinada y factor reumatoide en participantes con artritis reumatoide. Por el contrario, los niveles de proteína C reactiva aumentaron en ambos grupos, pero fueron más altos en el grupo de artritis reumatoide. Los parámetros periodontales en los participantes con artritis reumatoide bajo fármacos antirreumáticos modificadores de la enfermedad presentaron una mejoría ligeramente mayor (p <0.05). Conclusiones: La terapia periodontal no quirúrgica tiene mejoras similares en los parámetros periodontales en pacientes con y sin artritis reumatoide. Además, la terapia periodontal no quirúrgica puede beneficiar los niveles séricos de anticuerpos anti-proteína citrulinada y factor reumatoide en pacientes con artritis reumatoide. NCT04658615.

Effects of nonsurgical periodontal therapy in patients with rheumatoid arthritis: a prospective before and after study.

Background: periodontal therapy has been suggested to have systemic effects. However, studies of periodontal therapy in rheumatoid arthritis patients have produced controversial results. Aim: To compare the effects of nonsurgical periodontal therapy on biochemical markers of rheumatoid arthritis and periodontal parameters in patients with and without rheumatoid arthritis. Methods: a prospective before-and-after study was conducted that included 21 participants without and 29 participants with rheumatoid arthritis. Periodontal parameters, Porphyromonas gingivalis detection, C-reactive protein, rheumatoid factor and anti-citrullinated protein antibodies were measured at baseline and three months after nonsurgical periodontal therapy and the changes were statistically assessed. Results: In general, both groups presented statistically significant improvement in periodontal parameters (p<0.05). There was an increase in the counts of P. gingivalis in both groups at three months. In addition, there was a reduction in levels of anti-citrullinated protein antibodies and rheumatoid factor in participants with rheumatoid arthritis. In contrast, C-reactive protein levels increased in both groups but were higher in the rheumatoid arthritis group. Periodontal parameters in rheumatoid arthritis participants under disease-modifying antirheumatic drugs presented a slightly higher improvement (p <0.05). Conclusions: Nonsurgical periodontal therapy has similar improvements in periodontal parameters in patients with and without rheumatoid arthritis. In addition, nonsurgical periodontal therapy may benefit serum levels of anti-citrullinated protein antibodies and rheumatoid factors in patients with rheumatoid arthritis. NCT04658615.

Antecedentes: se ha sugerido que la terapia periodontal tiene efectos sistémicos. Sin embargo, los estudios de la terapia periodontal en pacientes con artritis reumatoide han producido resultados controvertidos. Objetivo: comparar los efectos de la terapia periodontal no quirúrgica sobre los marcadores bioquímicos de la artritis reumatoide y los parámetros periodontales en pacientes con y sin artritis reumatoide. Métodos: se realizó un estudio prospectivo de antes y después que incluyó a 21 participantes sin artritis reumatoide y 29 participantes con artritis reumatoide. Se midieron los parámetros periodontales, detección de Porphyromonas gingivalis, proteína C reactiva, factor reumatoide y anticuerpos anti-proteína citrulinada al inicio del estudio y tres meses después de la terapia periodontal no quirúrgica y los cambios se evaluaron estadísticamente. Resultados: En general, ambos grupos presentaron mejoría estadísticamente significativa en los parámetros periodontales (p <0.05). Hubo un aumento en los recuentos de P. gingivalis en ambos grupos a los tres meses. Además, hubo una reducción en los niveles de anticuerpos anti-proteína citrulinada y factor reumatoide en participantes con artritis reumatoide. Por el contrario, los niveles de proteína C reactiva aumentaron en ambos grupos, pero fueron más altos en el grupo de artritis reumatoide. Los parámetros periodontales en los participantes con artritis reumatoide bajo fármacos antirreumáticos modificadores de la enfermedad presentaron una mejoría ligeramente mayor (p <0.05). Conclusiones: La terapia periodontal no quirúrgica tiene mejoras similares en los parámetros periodontales en pacientes con y sin artritis reumatoide. Además, la terapia periodontal no quirúrgica puede beneficiar los niveles séricos de anticuerpos anti-proteína citrulinada y factor reumatoide en pacientes con artritis reumatoide. NCT04658615.

Artrite reumatoide do tipo EORA com trombocitose significativa: relato de caso / Elderly-onset rheumatoid arthritis with significant thrombocytosis: a case report

Este relato teve como objetivo apresentar um caso de elderly onset rheumatoid arthritis associada à trombocitose reacional significativa. À admissão, o paciente apresentava quadro de poliartrite de pequenas e grandes articulações associado à rigidez matinal. Após exames solicitados, evidenciaram-se trombocitose de 1.697.000 cel./mm³ e anticorpos antipeptídeos citrulinados positivos, sendo diagnosticado com artrite reumatoide do tipo elderly onset rheumatoid arthritis.

This report aimed at presenting a case of elderly-onset rheumatoid arthritis associated with significant reactive thrombocytosis. On admission, the patient presented polyarthritis of small and large joints associated with morning stiffness. After the performance of the requested tests, thrombocytosis of 1,697,000 cells/mm3 and positive anti-CCP were evidenced, and the patient was diagnosed with elderly-onset rheumatoid arthritis.

Artritis reumatoide, diagnóstico, evolución y tratamiento / Rheumatoid arthritis, diagnosis, evolution and treatment

La artritis reumatoide es la enfermedad inflamatoria más común en adultos con una alta prevalencia en la población general, invocando para su diagnóstico la presencia de al menos cuatro criterios de los orientados por el Colegio Americano de Reumatología, teniendo un papel protagónico en los últimos años la presencia de anticuerpos anti proteína citrulinada, así como los estudios de imágenes, que ayudan al diagnóstico de la artritis reumatoide temprana en el curso de los dos primeros años de evolución y sus orientaciones terapéuticas adecuadas, aspecto fundamental en la actualidad para evitar las lesiones erosivas irreversibles, que resultan en un marcado compromiso de la calidad de vida de los pacientes que la sufren, elementos que revisamos en este artículo de opinión(AU)

Rheumatoid arthritis is the most common inflammatory disease in adults with a high prevalence in the general population, invoking for its diagnosis the presence of at least four criteria of those guided by the American College of Rheumatology, having a leading role in recent years the presence of anti-citrullinated protein antibodies, as well as imaging studies, which help the diagnosis of early rheumatoid arthritis in the course of the first two years of evolution and its appropriate therapeutic orientations, a fundamental aspect nowadays to avoid irreversible erosive lesions , which result in a marked commitment to the quality of life of patients who suffer from it, elements that we review in this opinion article(AU)

Are obesity, ACPAs and periodontitis conditions that influence the risk of developing rheumatoid arthritis in first-degree relatives?

The aim of this study was to investigate the body mass index (BMI), anti-citrullinated protein antibodies (ACPAs) status and the presence of periodontitis and IgG-1/IgG-2 antibodies against Porphyromonas gingivalis (Pg) in the first-degree relatives (FDRs) of rheumatoid arthritis (RA) patients and compare these variables with a control group of healthy individuals from the general population. In total, 100 FDR individuals and 200 healthy controls matched by age and gender were included. Rheumatologic and periodontal assessment was performed, and the presence of ACPAs and anti-P. gingivalis antibodies was evaluated. Groupwise comparisons were analysed using the McNemar and Wilcoxon tests. A conditional logistic regression analysis was performed to establish the associations between BMI, ACPAs and periodontitis in both groups. In the FDR group, 70% of the subjects were female, with a mean age of 37.3 ± 13 years. Obesity was observed in 17 and 7% of the FDRs and controls, respectively. ACPAs were found in 7% of the FDRs vs. 2.5% of the controls. Periodontitis was diagnosed in 79 and 56% of the FDRs and controls, respectively. Among the FDRs, 15% had severe periodontitis. There were associations in the FDR group related to the presence of obesity (OR 2.93, 95% CI 1.03-8.28), ACPAs (OR 2.45, 95% CI 0.7-8.32) and periodontitis (OR 3.70 95% CI 1.89-7.29). Regarding anti-P. gingivalis antibodies and smoking history, no differences were found between the groups. Obesity, ACPAs and periodontitis (diagnosis and severity) can be considered as relevant conditions associated with the development of RA in FDRs.

Hearing impairment in patients with rheumatoid arthritis: association with anti-citrullinated protein antibodies.

It has been suggested that hearing impairment (HI) is one of the extra-articular features of rheumatoid arthritis (RA). Nevertheless, the prevalence and nature of HI in RA is still uncertain. The objectives were to study hearing function in patients with RA using audiometric tests and to examine whether HI correlates with autoantibodies. Hearing functions were investigated in 43 consecutive RA patients and 23 control subjects (less than 60 years old). Their sera were evaluated for the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and anti-mutated citrullinated vimentin (anti-MCV) antibodies. HI was observed in 46.5 % of RA patients and in 30.4 % of control subjects, p = 0.32. HI was characterized as sensorineural in 80 and 85.7 % of RA patients and control subjects with HI, respectively, p = 1.00. RA patients had a worse hearing threshold for air conduction at 6 kHz in the right ear (p = 0.019) and had a decreased amplitude of otoacoustic emissions (OAEs) at 2 kHz bilaterally (p = 0.04) compared with control subjects. In the RA group, patients with and without HI were 80 and 34.78 % anti-CCP positive, respectively, p = 0.008. RA patients with and without HI were 85 and 43.48 % anti-MCV positive, respectively, p = 0.013. HI in RA patients was mainly sensorineural and was associated with anti-CCP and anti-MCV antibodies.

The amount of citrullinated proteins in synovial tissue is related to serum anti-cyclic citrullinated peptide (anti-CCP) antibody levels.

The objective of this study was to determine the relationship between citrullinated proteins in synovial tissue with peripheral anti-citrullinated peptides autoantibodies (ACPA) and peptidylarginine deiminase (PADI) PADI2, PADI3, and PADI4 messenger RNA (mRNA) expressions in synovial tissue and fibroblast-like synoviocytes in rheumatoid arthritis (RA) patients. Eleven RA and 12 osteoarthritis (OA) patients who underwent knee replacement surgery were studied. We detected citrullinated proteins in synovial tissue homogenates by western blot and serum ACPA by ELISA to anti-cyclic citrullinated peptide (anti-CCP) antibodies, and PADI2, PADI3, and PADI4 mRNA expressions in synovial tissue and in fibroblast-like synoviocytes. Patients with high amount of citrullinated proteins in synovial tissue (3 out of 7) have high levels of anti-CCP in serum. However, in the remaining 4 patients, the amount of synovial citrullinated proteins was minimal and their sera showed low levels of anti-CCP antibodies. Furthermore, we observed an increase in PADI2 mRNA expression in RA synovial tissue compared with OA patients (p = 0.02). We detected PADI3 mRNA in the synovial tissue of RA patients, but not in the tissue of OA patients. Even though fibroblast-type synoviocytes in RA are not the main source of PADs in the synovial tissue, they express PADI2 mRNA moderately, PADI4 mRNA weakly, while there is no detectable expression of PADI3 mRNA. In conclusion, we found a variety of citrullinated proteins in the synovial tissue of RA patients and the amount of such proteins is related to serum concentration of anti-CCP antibodies. We identified the presence of PADI3 mRNA expression in synovial tissue and PADI2 and PADI4 mRNA expressions in fibroblast-like synoviocytes from patients with RA.