Influenza A/Singapore (H3N2) component vaccine in systemic lupus erythematosus: A distinct pattern of immunogenicity.

INTRODUCTION: Influenza A (H3N2) virus is the most important cause of seasonal influenza morbidity and mortality in the last 50 years, surpassing the impact of H1N1. Data assessing immunogenicity and safety of this virus component are lacking in systemic lupus erythematosus (SLE) and restricted to small reports with other H3N2 strains. OBJECTIVE: This study aims to evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in SLE. METHODS: 81 consecutive SLE patients and 81 age- and sex-matched healthy controls (HC) were vaccinated with the influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers(GMT), and factor increase in GMT(FI-GMT) and adverse events were assessed before and 4 weeks post-vaccination. Disease activity and therapies were also evaluated. RESULTS: Before immunization, SLE and HC groups had high SP rates (89% vs 77%, p = 0.061) and elevated GMT titer with higher levels in SLE (129.1(104.1-154.1) vs 54.8(45.0-64.6), p < 0.001). Frequency of two previous years' influenza vaccination was high and comparable in SLE and HC (89% vs 90%, p = 1.000). Four weeks post-vaccination, median GMT increased for both groups and remained higher in SLE compared to HC (239.9(189.5-290.4) vs 94.5(72.6-116.4), p < 0.0001) with a comparable FI-GMT (2.3(1.8-2.9) vs 1.9(1.5-2.3), p = 0.051). SC rates were low and comparable for both groups (16% vs 11%, respectively, p = 0.974). Disease activity scores remained stable throughout the study (p = 1.000) and severe adverse events were not identified. CONCLUSION: Influenza A/Singapore (H3N2) vaccine has an adequate safety profile. The distinct immunogenicity pattern from other influenza A components characterized by a remarkably high pre- and post-vaccination SP rate and high GMT levels may be associated with previous influenza A vaccination. (www.clinicaltrials.gov, NCT03540823).

Clues for previously undiagnosed connective tissue disease in patients with trigeminal neuralgia.

BACKGROUND: Connective tissue diseases (CTD) may be associated with idiopathic trigeminal neuralgia (TN). The prevalence and diagnostic implications of this association are, however, not well established. OBJECTIVES: The objective of this study was to evaluate, in TN patients, if rheumatologic clinical and laboratory findings could contribute to the early diagnosis of rheumatic diseases. METHODS: Forty-six consecutive TN patients, 67% female, mean disease duration 8.78 +/- 7.25 years, and 47 controls were initially interviewed using a standard questionnaire based on common signs/symptoms of systemic lupus erythematosus, Sjögren syndrome, mixed CTD, and systemic sclerosis. Autoantibodies were detected by standard techniques. Those with rheumatologic complaints or positive autoantibodies were referred to the Rheumatology Outpatient Clinic for a more detailed evaluation. Secondary causes of TN were excluded. RESULTS: The frequency of Raynaud phenomenon (P = 0.026) and ANA reactivity (P = 0.04) were significantly higher in TN patients compared with controls. Fourteen TN patients were ANA positive. Seven of them reported concomitant rheumatic complaints, and interestingly, diffuse CTD was diagnosed in 4 (57%) of these patients: 1 systemic lupus erythematosus; 2 Sjögren syndrome; and 1 undifferentiated disease with scleritis and positive parotid scintigraphy. In all cases, TN preceded by at least 10 months the rheumatologic signs/symptoms. Moreover, these 4 TN patients with CTD had a higher frequency of sicca symptoms (P = 0.001) and higher titers of ANA (>or=1:320) (P = 0.006) than the remaining 42 TN patients without CTD diagnoses. Sixteen patients had isolated laboratory or clinical abnormalities, and none of them had CTD diagnoses. CONCLUSIONS: The concomitant presence of sicca symptoms and high titer ANA are clues for the early investigation of rheumatic diseases in TN patients.

Collagen V nasal tolerance in experimental model of systemic sclerosis.

Our aim was to study skin remodeling and autoantibody production in an experimental model of scleroderma (SSc), following nasal tolerance with human type V collagen (Col V). Female New Zealand rabbits (n = 12) were immunized with two doses of 1 mg/ml of Col V in complete Freund's adjuvant and additional two boosters in incomplete Freund's adjuvant to induce SSc. After 150 days, half of these immunized rabbits were submitted to type V collagen-induced tolerance receiving a daily nasal administration of 25 mug of Col V. Control animals (n = 6) were only submitted to type V collagen-induced tolerance. Serial skin biopsies were performed on days 0, 150 and 210, and stained with H&E, Masson's trichrome and Picrosirius for morphological and morphometric analysis. Types I, III and V collagen were identified by immunofluorescence. The animals' serum samples were collected to determine anti types I, III, IV and V collagen and antinuclear antibodies (ANA). Skin biopsies from immunized animals confirmed SSc morphology as previously described, such as progressive decrease of papillary dermis, appendages atrophy, increased type I, III and V collagen deposition. Rabbits with Col V-induced nasal tolerance showed reduction of skin involvement, with significant decrease of collagen amount. Humoral immune response did not change with nasal tolerance. Collagen V nasal tolerance promotes regression of skin remodeling process in an experimental model of SSc. We suggest that nasal tolerance with type V collagen can be a promising therapeutic option to treat scleroderma patients.

Celiac disease associated with nodular regenerative hyperplasia, pulmonary abnormalities, and IgA anticardiolipin antibodies.

The association of nodular regenerative hyperplasia with celiac disease is not as well established as it is with hepatopulmonary syndrome and portopulmonary hypertension. IgA anticardiolipin antibodies were reported recently in celiac patients with nodular regenerative hyperplasia. The subject of this study was the description of pulmonary abnormalities and IgA anticardiolipin antibodies in celiac patients with noncirrhotic portal hypertension. Five patients with portal hypertension were investigated to diagnose its etiology. Celiac disease was diagnosed by means of autoantibody reactivity and duodenal biopsies. Liver histology revealed nodular regenerative hyperplasia in four patients and suggested its presence in 1 case. Two cyanotic patients had severe hypoxemia with a confirmed diagnosis of hepatopulmonary syndrome. Another case exhibited features of hepatopulmonary syndrome with increased levels of arterial pulmonary pressure. The remaining 2 cases had slight abnormalities of arterial oxygenation. Three patients had reactivity to IgA anticardiolipin antibodies. The concomitance of celiac disease and nodular regenerative hyperplasia, two infrequent conditions, raises suspicion of there being a nonfortuitous coincidence. Pulmonary abnormalities, and especially hepatopulmonary syndrome, are described for the first time in association with celiac disease and nodular regenerative hyperplasia.

Metodos laboratoriais para a deteccao dos anticorpos anti-Ro/SSA e anti-La/SSB / Methods for detection of anti-Ro/SSA and anti-La/SSB antibodies

Determinamos neste trabalho a sensibilidade e especificidade da imunofluerescencia, imunodifusao, contraimunoeletroforese (CIE) e "Western blotting" (WB) para a deteccao dos anticorpos anti-Ro/SSA e anti-La/SSB. Todos os soros positivos para estes anticorpos apresentaram imunofluorescencia nuclear positiva, no entanto este teste mostrou totalmente inespecifico. A CIE foi o melhor metodo para a deteccao do anticorpo anti-Ro/SSB. O WB tem sensibilidade inferior mas demonstrou que a resposta ao antigeno Ro/SSA de 50kD predominou no lupus eritematoso sistemico (SLE). Em contraste, o WB e o metodo mais sensivel e especifico para a deteccao do anticorpo anti-La/SSB, seguidos pela CIE e imunodifusao. Os anticorpos anti-Ro/SSA e o anti-La/SSB foram os que estiveram mais frequentemente associados. Apenas 6 soros anti-Ro/SSA possuiam este anticorpo isoladamente e nenhum apresentou a imunofluorescencia nuclear negativa