Long-Term Follow-Up of Anti-Infliximab Antibodies in Patients With Radiographic Axial Spondyloarthritis: A Marker of Drug Survival and Tapering.

OBJECTIVE: The aim of this study was to evaluate the influence of anti-infliximab (IFX) antibodies on three different points of care: response/tolerance to IFX, tapering strategy, and in a subsequent treatment with a second tumor necrosis factor inhibitor (TNFi). METHODS: A prospective cohort of 60 patients with radiographic axial spondyloarthritis who received IFX were evaluated retrospectively regarding clinical/laboratorial data, IFX levels, and anti-IFX antibodies at baseline, after 6, 12 to 14, 22 to 24, 48 to 54, 96 to 102 weeks, and before tapering or switching. RESULTS: Anti-IFX antibodies were detected in 27 patients (45%), of whom 23 (85.1%) became positive in the first year of IFX treatment. In comparison to the group that was negative for anti-IFX antibodies, patients who were positive for anti-IFX antibodies demonstrated the following: less use of methotrexate as a concomitant treatment to IFX (5 [18.5%] vs 14 [42.4%]; P = 0.048), more infusion reactions at 22 to 24 weeks (P = 0.020) and 48 to 54 weeks (P = 0.034), more treatment failures (P = 0.028) at 48 to 54 weeks, reduced overall IFX survival (P < 0.001), and lower sustained responses (P = 0.044). Of note, patients who were positive for anti-IFX antibodies exhibited a shorter tapering survival (9.9 months [95% confidence interval (CI) 4.0-15.8] vs 63.4 months [95% CI 27.9-98.8]; P = 0.004) in comparison with patients who were negative for anti-IFX antibodies. Conversely, for patients who failed IFX, patients who were positive for anti-IFX antibodies had better clinical response to the second TNFi at three months (15 [83.3%] vs 3 [27.3%]; P = 0.005) and six months (15 [83.3%] vs 4 [36.4%]; P = 0.017) than the patients who were negative for anti-IFX antibodies after switching. CONCLUSION: This study provided novel data that anti-IFX antibodies is a parameter for reduced tapering survival, reinforcing its detection to guide clinical decision. Additionally, we confirmed in a long-term cohort the anti-IFX antibody association with worse IFX performance and as predictor of the second TNFi good clinical response.

Primary dental care treatment in primary Sjögren's syndrome: a possible role in improving salivary flow rate.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is an inflammatory chronic disorder that mainly affects exocrine glands. Additionally, oral infections can aggravate the glandular dysfunction. However, data on primary dental care (PDC) treatment in pSS are scarce. This study aimed to appraise the impact of PDC on the Xerostomia Inventory (XI), unstimulated/stimulated salivary flow rates and salivary cytokine profile in pSS. METHODS: Fifty-two pSS patients and 52 sex- and age-matched control participants without systemic autoimmune diseases were included in a prospective study. At inclusion, all participants were assessed through a standardised protocol, measurement of salivary pro-inflammatory cytokines, and underwent PDC. Dental procedures included: oral hygiene guidance, restorative treatment of caries, surgical removal of residual roots and impacted or partially erupted teeth, cysts, supra and subgingival periodontal scaling and treatment of soft tissue disorders (removal of lesions and treatment of opportunistic infections). After 3 months, the clinical/laboratorial assessments were repeated. RESULTS: At inclusion, the Decayed, Missing and Filled Teeth (DMFT) index was higher in the pSS patients than in the control group (13.3±8.2 vs. 8.6±6.2, p=0.002), whereas periodontal parameters were comparable in both groups (p>0.05). After PDC, 26.9% of pSS patients showed a reduction of at least 6 points (clinical improvement) in XI, but mean XI remained unchanged (p=0.285). PDC resulted in an increase in mean unstimulated (p<0.001) and stimulated (p=0.001) salivary flow rates in pSS, with no change in salivary cytokine profile (p≥0.05). CONCLUSIONS: PDC promoted improvement in unstimulated and stimulated salivary flow rates in pSS. This novel finding reinforces the recommendation of this strategy for pSS patients. CLINICALTRIALS: gov (Identifier: NCT03711214).

Abatacept induced long-term non-progressive reduction in gamma-globulins and autoantibodies: dissociation from disease activity control.

OBJECTIVES: To evaluate long-term effects on gamma-globulins and autoantibodies of abatacept (ABA) versus tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients. METHOD: Eighteen RA patients undergoing abatacept (ABA-RA) and 18 age/sex-matched patients treated with TNFi (TNFi-RA) were compared regarding clinical data, total gamma-globulins (TGG), specific subtypes (IgG, IgM, IgA), free light chains (FLC), IgM/IgG rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP3), and anti-mutated citrullinated vimentin (anti-MCV), assessed before and every 6 months, up to 24 months. EXCLUSION CRITERIA: previous abatacept/rituximab or low TGG (< 0.7 g/dL). RESULTS: At baseline, female sex (78 vs. 78%), age (55 vs. 53 years), DAS28 (5.73 vs. 5.67), TGG (1.4 vs. 1.35 g/dL), IgG (1168 vs. 1079 mg/dL), IgM (107 vs. 113 mg/dL), IgA (333 vs. 322 mg/dL), kappa (342 vs. 249 mg/dL), lambda (170 vs. 150 mg/dL), IgM-RF (76 vs. 53 UI), IgG-RF (63 vs. 25 UI), anti-CCP3 (216 vs. 189 UI), and anti-MCV (202 vs. 102 UI) were comparable in ABA-RA and TNFi-RA (p > 0.05). Similar disease activity improvement was observed in both groups. In ABA-RA, significant decreases (p < 0.05) were observed in TGG (1.4 vs. 1.05 g/dL), IgG (1168 vs. 997), IgA (333 vs. 278 mg/dL), kappa (342 vs. 257 mg/dL), lambda (170 vs. 144 mg/dL), IgM-RF (76 vs. 37 UI), IgG-RF (65 vs. 24 UI), anti-CCP3 (216 vs. 183 UI), and anti-MCV (202 vs. 60 UI) at 6 months, without further decreases. In contrast, TNFi-RA showed no decrease in any of such parameters. ABA-RA also had more often transient IgG levels under the lower limit of normality (66.7% vs. 33.3%, p = 0.046). No severe infection occurred. DAS28, ESR, and CRP correlated significantly to gamma-globulins and FLC at baseline (p < 0.05), but these correlations were longitudinally lost in ABA-RA, but not in TNFi-RA. CONCLUSION: ABA, but not TNFi, induces a safe, persistent, long-term, and non-progressive reduction in gamma-globulins and autoantibodies, including anti-MCV. This pattern is dissociated from disease activity control.Key Points• ABA induces a long-term and non-progressive reduction in gamma-globulins and FLC, which occurs regardless of disease activity control.• ABA-induced reduction in gamma-globulins and FLC promotes a dissociation of such parameters and disease activity.• The same pattern of reduction is observed in autoantibodies: IgM-RF, IgG-RF, anti-CCP3, and anti-MCV.• Low transient IgG can be observed in RA patients treated with ABA, but does not correlate to infection.

Ovarian reserve in young juvenile idiopathic arthritis patients.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) occurs during reproductive age, however, there are no systematic data regarding ovarian function in this disease. METHODS: Twenty-eight post-pubertal JIA patients and age-matched 28 healthy controls were studied. Complete ovarian function was assessed during the early follicular phase of the menstrual cycle including anti-Müllerian hormone (AMH), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) by ovarian ultrasound, and anti-corpus lutheum antibodies (anti-CoL). Demographic data, menstrual abnormalities, disease parameters and treatment were also evaluated. RESULTS: The mean current age (22.6 ± 6.59 vs. 22.5 ± 6.59 years, p = .952) was similar in JIA patients and healthy controls with a higher median menarche age [13(8-16) vs. 12(8-14) years, p = .029]. A lower median AMH levels [2.65(0.47-9.08) vs. 4.83(0.74-17.24) ng/mL, p = .029] with a higher LH [8.44 ± 4.14 vs. 6.03 ± 2.80 IU/L, p = .014] and estradiol levels [52.3(25.8-227.4) vs. 38.9(26.2-133.6) pg/mL, p = .008] were observed in JIA compared to control group. Anti-CoL and AFC were similar in both groups (p > .05). Further analysis of JIA patients revealed that current age, disease duration, number of active/limited joints, ESR, CRP, patient/physician VAS, JADAS 71, DAS 28, CHAQ, HAQ, patient/parents PedsQL, PF-SF 36, cumulative glucocorticoid and cumulative methotrexate doses were not correlated with AMH, FSH, estradiol levels or AFC (p > .05). CONCLUSION: The present study was the first to suggest diminished ovarian reserve, not associated to hypothalamic pituitary gonadal axis, in JIA patients during reproductive age. The impact of this dysfunction in future fertility of these patients needs to be evaluated in prospective studies.

The clinical spectrum of antinuclear antibodies associated with the nuclear dense fine speckled immunofluorescence pattern.

OBJECTIVE: Autoantibodies to lens epithelium-derived growth factor (LEDGF) depict a distinctive nuclear dense fine speckled (DFS) pattern in the indirect immunofluorescence antinuclear antibody assay (IIF-ANA). Definition of the clinical spectrum associated with anti-LEDGF antibodies has been evolving over the last decade. We investigated the frequency, clinical spectrum, and immunologic specificity of the DFS pattern in a general clinical laboratory routine. METHODS. All serum samples entered for IIF-ANA determination within a 2 year period were examined for the DFS pattern. Positive samples with consistent clinical information were studied further by IIF with isotype-specific conjugate and immunoblot analysis. RESULTS: Among 13,641 ANA-positive samples, 5081 (37%) presented the DFS pattern. Within a 6 month nested period, there were 650 samples with DFS pattern, and consistent clinical data were available for 81 of these. DFS reactivity was mainly due to IgG. Most samples (86%) presented titer > or = 1/640. Eighty of the 81 DFS samples reacted with a 75 kDa band that comigrated with the band elicited by the standard anti-LEDGF serum. Antibodies that were affinity-purified from the 75 kDa band reproduced the DFS pattern on IIF-ANA. The clinical spectrum associated with DFS reactivity included autoimmune diseases (39%) and an array of nonautoimmune conditions (61%). Among the autoimmune patients, over half presented evidence of autoimmune thyroiditis. CONCLUSION: Anti-LEDGF/p75 antibodies are a common finding among ANA-positive individuals with no evidence of rheumatic autoimmune disease, and should be regarded as a low specificity finding even when in moderate or high titer.

Endometriosis and systemic lupus erythematosus: a comparative evaluation of clinical manifestations and serological autoimmune phenomena.

PROBLEM: In view of evidences suggesting association between endometriosis (EM) and systemic lupus erythematosus (SLE), we have performed a comparative evaluation of clinical and humoral immunologic abnormalities in both diseases. METHOD OF STUDY: Forty-five women (18-40 years) with histologically confirmed pelvic EM, 21 healthy-women and 15 female SLE-patients (18-40 years) without surgically confirmed EM were prospectively evaluated. Immunologic investigations were performed by blinded researchers. RESULTS: None of the EM-patients fulfilled criteria for SLE. However, EM-patients presented higher frequencies of arthralgia (62%) and generalized myalgia (18%) superior than normal-controls (24%, P = 0.004/0%, P = 0.048) but comparable with SLE-patients (33%, P = 0.052/27%, P = 0.5). Similarly to SLE (7%), 9% of EM-patients presented fibromyalgia. Antinuclear antibodies (ANA) were detected in 18% of EM-sera, as compared with healthy-women (0%, P = 0.014) and SLE-patients (93%, P = 0.0005). In contrast with SLE, antibodies to dsDNA, Sm and U1RNP were negative in EM-sera. Anti-Ro and anticardiolipin antibodies were more often in SLE (40%, 33%) than in EM-patients (2%, P < 0.001/9%, P = 0.04). Elevated immune-complexes and low total complement were more frequent in SLE (40%, 13%) compared with EM-sera (7%, P = 0.005/0%, P = 0.01). CONCLUSIONS: Our data indicate differences of ANA antigenic specificity and complement consumption between EM and SLE. The high prevalence of generalized musculoskeletal complaints in EM justifies a multidisciplinary approach.

Doenca de Lyme em Mato Grosso do Sul: relato de tres casos clinicos, incluindo o primeiro caso de meningite de Lyme no Brasil / Lyme disease in Mato Grosso do Sul State, Brazil: report of three clinical cases, including the first of Lyme meningitis in Brazil

Os autores relatam a ocorrencia dos tres primeiros casos clinicos da Doenca de Lyme no Estado de Mato Grosso do Sul, incluindo o primeiro caso de meningite de Lyme no Brasil, identificados por criterios clinicos e labopratoriais. A pesquisa de anticorpos anti-Borrelia burgdorferi foi realizada atraves das tecnicas de ELISA e de Western Blotting, sendo que pela primeira tecnica apenas anticorpo da classe IgG foi identificado em um unico caso. Atraves do imunoblotting, encontrou-se no soro: cinco bandas para IgG e duas para IgM no primeiro caso; sete bandas para IgG e duas bandas para IgM no segundo caso; e no terceiro caso, cinco bandas para IgG e seis para IgM...