Characterizing hand and wrist ultrasound pattern in primary Sjögren's syndrome: a case-control study.

INTRODUCTION/OBJECTIVES: To evaluate the clinical relevance of high-resolution hand and wrist ultrasound (US) findings and their possible associations with anti-citrullinated peptide antibodies in primary Sjögren's syndrome (pSS). METHODS: Ninety-seven consecutive pSS patients (American-European Consensus Group, 2002) without meeting the American College of Rheumatology (ACR) criteria (1987) for rheumatoid arthritis (RA); 20 RA patients (ACR/European League Against Rheumatism (EULAR) criteria, 2010); and 80 healthy individuals with comparable age, gender, and ethnicity were enrolled in a case-control study. Disease activity was assessed by EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). US was performed by one expert blinded to anti-CCP, anti-MCV, and IgM rheumatoid factor tested by ELISA. RESULTS: Frequencies of grade 3 synovitis (9.3 vs. 0%, p = 0.004), tenosynovitis (36.1 vs. 3.8%, p < 0.001), and erosions (27.8 vs. 7.5%, p = 0.001) on US were higher in pSS patients than in healthy controls. ESSDAI presented a moderate correlation with the synovitis number (p = 0.001) and tenosynovitis (p < 0.001). Most pSS patients with erosions on US (81.5%) had negative anti-CCP. Nevertheless, anti-CCP ≥ 3× cut-off value was associated with the presence of erosions in pSS (p = 0.026). Erosions in pSS were mainly small size contrasting with moderate/large size in RA (p < 0.001), and positive power Doppler synovitis predominated in RA (p < 0.001). CONCLUSIONS: US identified significant frequencies of grade 3 synovitis, tenosynovitis, and erosions in pSS. Synovitis and tenosynovitis numbers were correlated with ESSDAI. Association between erosions on US and anti-CCP (high titers) in pSS possibly identifies a subgroup with severe arthritis. These findings suggest that US is a useful method for assessing joint involvement in pSS.Key Points• US identified significant frequencies of grade 3 synovitis, tenosynovitis, and erosions in pSS patients in comparison with age- and race-healthy individuals.• Numbers of synovitis and tenosynovitis on US were correlated with ESSDAI values.• Most pSS patients with erosions on US were negative for anti-CCP, but anti-CCP ≥ 3× cut-off value was associated with the presence of erosions in this disease.• Erosions in pSS were mainly small size contrasting with moderate/large size in RA, and positive power Doppler synovitis predominated in RA.

Ovarian reserve in women with primary antiphospholipid syndrome.

OBJECTIVE: The objective of this paper is to evaluate ovarian reserve in primary antiphospholipid syndrome (PAPS) women and the association between ovarian reserve tests and clinical and laboratorial parameters, and anti-corpus luteum antibody (anti-CoL). METHODS: We screened 85 female patients between 18 to 40 years old with APS. Of these, 67 patients were excluded because of association with other autoimmune diseases (n = 42), contraindication or unwillingness to stop hormonal contraceptive (n = 21), current pregnancy or breastfeeding (n = 3) and previous ovarian surgery (n = 1). Therefore, a cross-sectional study was conducted in 18 PAPS patients and 24 healthy women. They were evaluated at early follicular phase with measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Müllerian hormone (AMH) and sonographic antral follicle count (AFC). Serum measurement of anti-CoL was determined by immunoblot analysis. All analyses were performed after at least six months from the last intake of hormonal contraceptive and resumption of menstruation. RESULTS: The mean age was comparable in PAPS and controls (33.0 ± 5.0 vs. 30.4 ± 7.0 years; p = 0.19). Regarding ovarian reserve tests, the frequencies of low AFC (≤10) (56% vs. 22%, p = 0.04) and very low AFC (≤5) (37% vs. 9%, p = 0.04) were significantly higher in PAPS patients than controls. Trends of higher frequencies of reduced (<1.0 ng/ml), low (<0.5 ng/ml) and negligible (<0.2 ng/ml) AMH levels were found in PAPS patients (p = 0.08, p = 0.07 and p = 0.07, respectively). FSH, LH and estradiol were similar in patients and controls. There was no association between low ovarian reserve and specific types of antiphospholipid antibodies. Anti-CoL was solely observed in PAPS patients (11% vs. 0%; p = 0.177) and was not related to ovarian reserve tests. CONCLUSION: Women suffering from PAPS possessed reduced ovarian reserve, with prevalence greater than 50%.

Podocyte injury in pure membranous and proliferative lupus nephritis: distinct underlying mechanisms of proteinuria?

Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte injury. Analysis of podocyte biomarkers was performed attempting to identify if podocyte phenotype is distinct in pure membranous and proliferative LN. Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by immunohistochemistry. Preserved synaptopodin expression was observed in only 10 (19.2%) of all biopsies while 42 (80.8%) had reduced expression. Both groups had comparable proteinuria at the time of biopsy (p = 0.22); however, in the mean follow-up of four years there was a tendency toward lower mean levels of proteinuria in patients with preserved synaptopodin staining (0.26±0.23 vs. 0.84±0.90 g/24 h, p = 0.05) compared with those with diminished expression. Thirty-nine (75%) biopsies were classified as proliferative and 13 (25%) as pure membranous. Comparison of podocyte biomarkers demonstrated a predominance of preserved staining of synaptopodin (69.2%), WT1 (69.2%), GLEPP1 (53.9%) and nephrin (60%) in the pure membranous group whereas only <10% of the proliferative showed preserved expression. Our data suggest that in proliferative forms there seems to occur structural podocyte damage, whereas in the pure membranous the predominant preserved pattern suggests a dysfunctional podocyte lesion that may account for the better long-term prognosis of proteinuria outcome.

High-titer antichromatin antibody is associated with proliferative class IV of lupus nephritis.

The antichromatin antibody (aCT) has been described as a useful marker for lupus nephropathy. The relevance of its nephritogenic potential may be appropriately evaluated in the context of renal histopathology. Therefore, the present study investigated the relationship of aCT with a particular histopathologic class of lupus nephritis (LN). Seventy-eight consecutive patients with systemic lupus erythematosus (ACR criteria) and active nephritis who underwent renal biopsy from 1999 to 2004 and with available frozen serum sample obtained at the time of biopsy were selected. aCT was measured by ELISA, and anti-dsDNA was measured by indirect immunofluorescence (IIF) and by ELISA. All renal biopsies were revised in a blinded manner by the same expert renal pathologist. Charts were extensively reviewed for demographic and renal features obtained at the time of biopsy. The prevalence of aCT (>or=20 U) was 59% with a mean titer of 74.3 +/- 38.7 U. Both aCT-positive and aCT-negative groups of patients had similar age, gender distribution, duration of lupus, and duration of renal disease. Anti-dsDNA was detected by IIF in 29.5% and by ELISA in 42.3% of the patients. Concomitant presence of both antibodies was observed in 63% (29/46) [anti-dsDNA by ELISA] and 45.6% (21/46) [anti-dsDNA by IIF] of the patients. Lower serum levels of C3 (73% vs. 40%, P = 0.0058) and C4 (82% vs. 46.7%, P = 0.0021) were more commonly observed in aCT >or= 20 U patients compared to the aCT-negative group. It is important to note that the use of a higher cut-off value (>or=40 U) for aCT test revealed a predominance of class IV LN (58% vs. 33%, P = 0.039) in aCT >or= 40 U compared to aCT < 40 U group. The mean levels of proteinuria, serum albumin, and creatinine were markedly altered but were comparable in both groups (P >or= 0.05). One fourth (26.3%) of the 19 patients with class IV LN and aCT >or= 40 U had no detectable anti-dsDNA (ELISA). These data suggest that high-titer aCT seems to be a valuable biomarker for proliferative class IV of LN.

C-ANCA-positive IgG fraction from patients with Wegener's granulomatosis induces lung vasculitis in rats.

The aim of the present study was to analyse in rats the ability of C-ANCA-positive IgG fraction in triggering inflammatory response on pulmonary tissue. Wistar rats (n = 18) were injected via the the internal jugular vein with 20 mg of total C-ANCA-positive IgG fraction isolated from serum of three different Wegener's granulomatosis patients obtained before therapy. Similarly, control rats were treated with IgG fraction from two rheumatoid arthritis patients (n = 7), IgG from six normal human sera (n = 15) or saline (n = 18), respectively. Animals were sacrificed after 24h of injection for histological analysis of the lungs. Vasculitis and inflammatory infiltrate were consistently absent in rats injected with rheumatoid arthritis IgG or saline and in 14/15 of normal IgG treated animals. In contrast, marked vasculitis was observed in all 18 animals injected with C-ANCA-positive IgG fraction. The histological features were characterized by the presence of a perivascular pleomorphic cellular sheath, particularly around small vessels, endothelial adherence and diapedesis of polymorphonuclear leucocytes and presence of granuloma-like lesions. A dose-response relationship was observed between protein concentration of C-ANCA IgG sample and the intensity of the inflammatory response in the animals. In addition, IgG fraction with undetectable C-ANCA, obtained from one patient in remission after treatment, was not able to reproduce the pulmonary tissue alterations induced by its paired IgG that was positive for C-ANCA taken before therapy. The experimental model described herein may be useful to characterize more effectively the pathogenic mechanism of C-ANCA in Wegener's disease.

[Lyme disease in Mato Grosso do Sul State, Brazil: report of three clinical cases, including the first of Lyme meningitis in Brazil]. / Doença de Lyme em Mato Grosso do Sul: relato de três casos clínicos, incluindo o primeiro relato de meningite de Lyme no Brasil.

The authors report the occurrence of the first three clinical cases of Lyme disease in Mato Grosso do Sul State, including the first case of Lyme meningitis in Brazil. These were identified by clinical and laboratorial criteria. Anti-Borrelia burgdorferi antibody search was carried out through ELISA and Western Blotting techniques, the former providing identification of IgG class antibodies alone, in one only of those cases. Through Immunoblotting, the following features were found in serum: 5 IgG and 2 IgM bands for the first case; 7 IgG and 2 IgM bands for the second; and 5 IgG and 6 IgM bands for the third. In the latter, presence fo specific antibodies was searched in liquor, due to lymphomonocitary meningitis occurrence, and one IgM band was detected. After antibiotic therapy, all patients exhibited significant clinical and laboratorial improvement in their conditions along with symptom regression to the present moment.

Meningoencefalitis por Cryptococcus neoformans. / Meningoencephalitis by Cryptococcus neoformans

Cryptococcus neoformans es una etiologia que siempre debe plantearse en sujetos portadores de patologias del S.R.E., sometidos a corticoterapia e inmunosupresores y que presenten compromiso del S.N.C., en especial meningoencefalitis. Es necesario destacar la sencillez del procedimiento de busqueda directa del hongo en L.C.R. y la importancia de este hallazgo