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Objectives: The involvement of the gut microbiota in the pathogenesis of calcium nephrolithiasis has been hypothesised since the discovery of the oxalate-degrading activity of Oxalobacter formigenes, but never comprehensively studied with metagenomics. The aim of this case-control study was to compare the faecal microbiota composition and functionality between recurrent idiopathic calcium stone formers (SFs) and controls. Design: Faecal samples were collected from 52 SFs and 48 controls (mean age 48±11). The microbiota composition was analysed through 16S rRNA microbial profiling approach. Ten samples (five SFs, five controls) were also analysed with deep shotgun metagenomics sequencing, with focus on oxalate-degrading microbial metabolic pathways. Dietary habits, assessed through a food-frequency questionnaire, and 24-hour urinary excretion of prolithogenic and antilithogenic factors, including calcium and oxalate, were compared between SFs and controls, and considered as covariates in the comparison of microbiota profiles. Results: SFs exhibited lower faecal microbial diversity than controls (Chao1 index 1460±363vs 1658±297, fully adjusted p=0.02 with stepwise backward regression analysis). At multivariate analyses, three taxa (Faecalibacterium, Enterobacter, Dorea) were significantly less represented in faecal samples of SFs. The Oxalobacter abundance was not different between groups. Faecal samples from SFs exhibited a significantly lower bacterial representation of genes involved in oxalate degradation, with inverse correlation with 24-hour oxalate excretion (r= '0.87, p=0.002). The oxalate-degrading genes were represented in several bacterial species, whose cumulative abundance was inversely correlated with oxaluria (r= '0.85, p=0.02). Conclusions: Idiopathic calcium SFs exhibited altered gut microbiota composition and functionality that could contribute to nephrolithiasis physiopathology.

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To investigate the association between vitamin D deficiency (25-hydroxyvitamin D <20 ng/mL) and idiopathic calcium nephrolithiasis (ICN).

CaSR gene is a candidate for calcium nephrolithiasis. Single-nucleotide polymorphisms (SNPs) encompassing its regulatory region were associated with calcium nephrolithiasis.

Nutrition has been widely recognized to influence the risk of kidney stone formation. Therefore the aim of our study was to assess: a) whether usual diet of women with idiopathic calcium nephrolithiasis (ICN) living in Parma (Northern-Italy) is different compared to healthy controls, b) how their diet differs from Italian National guidelines and c) whether it is related to nephrolithiasis clinical course.

BACKGROUND: A direct relation exists between sodium and calcium excretion, but randomized studies evaluating the sustained effect of a low-salt diet on idiopathic hypercalciuria, one of the main risk factors for calcium-oxalate stone formation, are still lacking. OBJECTIVE: Our goal was to evaluate the effect of a low-salt diet on urinary calcium excretion in patients affected by idiopathic calcium nephrolithiasis. DESIGN: Patients affected by idiopathic calcium stone disease and hypercalciuria (>300 mg Ca/d in men and >250 mg Ca/d in women) were randomly assigned to receive either water therapy alone (control diet) or water therapy and a low-salt diet (low-sodium diet) for 3 mo. Twenty-four-hour urine samples were obtained twice from all patients: one sample at baseline on a free diet and one sample after 3 mo of treatment. RESULTS: A total of 210 patients were randomly assigned to receive a control diet (n = 102) or a low-sodium diet (n = 108); 13 patients (2 on the control diet, 11 on the low-sodium diet) withdrew from the trial. At the follow-up visit, patients on the low-sodium diet had lower urinary sodium (mean +/- SD: 68 +/- 43 mmol/d at 3 mo compared with 228 +/- 57 mmol/d at baseline; P < 0.001). Concomitant with this change, they showed lower urinary calcium (271 +/- 86 mg/d at 3 mo compared with 361 +/- 129 mg/d on the control diet, P < 0.001) and lower oxalate excretion (28 +/- 8 mg/d at 3 mo compared with 32 +/- 10 mg/d on the control diet, P = 0.001). Urinary calcium was within the normal range in 61.9% of the patients on the low-salt diet and in 34.0% of those on the control diet (difference: +27.9%; 95% CI: +14.4%, +41.3%; P < 0.001). CONCLUSION: A low-salt diet can reduce calcium excretion in hypercalciuric stone formers. This trial was registered at clinicaltrials.gov as NCT01005082.

A debate on updating the laboratory criteria of antiphospholipid syndrome (APS) was recently opened in view to lower the risk of over diagnosis of the syndrome. Based on data related to thrombotic APS, it proposes the exclusion of anticardiolipin antibodies (aCL) and anti-beta2-glycoprotein 1 (a-beta2-GPI) IgM detection. Here, we examine this possibility in a study which focuses on obstetrical APS (OAPS). We report new data on a prospective multicenter European cohort of 109 pregnant women having APS. Among them, 73 had purely obstetrical APS, not associated to autoimmune diseases or thrombosis. Isolated antibodies and isolated aCL positivity were present in 50/109 (46%) and in 34/109 (31%) of the women, respectively. An isolated a-beta2-GPI IgM was present in three women. These results suggest that aCL and a-beta2-GPI IgM cannot be dropped for the diagnosis and classification of OAPS. The low level of some antibodies associated with severe obstetrical complications raise the issue of keeping or not the same laboratory criteria for OAPS and for thrombotic APS and whether additional criteria after large prospective studies could further improve diagnosis.

Background: Antinucleosome antibodies (anti-NCS) are reported to be highly sensitive and specific for systemic lupus erythematosus (SLE) and to correlate with disease activity. They may appear in early stages of the disease, in particular before anti-dsDNA antibodies, being a potential marker for identifying patients susceptible to SLE. Patients with primary antiphospholipid syndrome (PAPS) may develop full-blown SLE but there is no evidence for markers predictive for that. Aim: To evaluate whether anti-NCS may be predictors for full-blown or lupus like disease (LL) in a cohort of PAPS patients. Methods: A multicentric cohort of 105 PAPS patients was tested for IgG/IgM anti-NCS by using a home made assay with H1-stripped chromatin as antigen. Results: Eighty-one out of 105 (77%) of the patients were positive for anti-NCS; medium-high titre results were present only in 49/105 (46%). Anti-NCS were more frequently detected in PAPS + LL, but no relationship with clinical/serological features was found, except for a weak correlation with anti-dsDNA antibodies. Two PAPS patients evolved into full-blown SLE during the follow-up and displayed high titre anti-NCS many years before. Conclusions: Our findings suggest that anti-NCS might be added to the mosaic of autoimmune phenomena characterizing PAPS patients and in particular those with more chance to evolve to SLE. © 2007 Elsevier Ltd. All rights reserved.

It was reported by several groups that patients diagnosed as primary antiphospholipid syndrome (PAPS) had developed a full-blown systemic lupus erythematosus (SLE) even after many years of follow-up. Little is known about clinical and/or serological factors that may help predict such evolution. Antinucleosome antibodies (anti-NCS) were described to appear in early stages of SLE, in particular before anti-dsDNA antibodies. The aim of the study is to evaluate the prevalence of anti-NCS in a large cohort of PAPS patients

Objective: Prothrombin (PT) is a target for antibodies with lupus anticoagulant (LA) activity, suggesting the possible application of anti-prothrombin antibody (aPT) assays in patients with antiphospholipid syndrome (APS). Different methods - both homemade and commercial - for the detection of aPT are available, but they seem to produce conflicting results. The purpose of this study was to compare the performance of different assays on a set of well-characterized serum samples. Patients and methods: Sera were gathered from 4 FIRMA institutions, and distributed to 15 participating centres. Forty-five samples were from patients positive for LA and/or anticardiolipin antibodies (aCL) with or without APS, and 15 were from rheumatoid arthritis (RA) patients negative for antiphospholipid antibodies. The samples were evaluated for IgG and IgM antibodies using a homemade direct aPT assay (method 1), a homemade phosphatidylserine-dependent aPT assay (aPS/PT, method 2), and two different commercial kits (methods 3 and 4). In addition, a commercial kit for the detection of IgG-A-M aPT (method 5) was used. Results: Inter-laboratory results for the 5 methods were not always comparable when different methods were used. Good inter-assay concordance was found for IgG antibodies evaluated using methods 1, 3, and 4 (Cohen k > 0.4), while the IgM results were discordant between assays. In patients with thrombosis and pregnancy losses, method 5 performed better than the others. Conclusion: While aPT and aPS/PT assays could be of interest from a clinical perspective, their routine performance cannot yet be recommended because of problems connected with the reproducibility and interpretation of the results

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium-the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors. © 2005 Elsevier B.V. All rights reserved.

The clinical impact of anti-DNA antibodies lies on their diagnostic power for systemic lupus erythematosus (SLE), being a formal classification criterion. In spite of such a disease association, low-avidity anti-DNA antibodies might also be part of the natural autoantibody repertoire.Their switch to pathogenic high-avidity autoantibodies is the result of the autoimmune process leading to SLE. Anti-DNA antibodies were shown to play a role in SLE pathogenesis and particularly in kidney damage. Accordingly, antibody titres might fluctuate in relation to disease activity, but their prognostic value for flares is still debated. Several methods for anti-DNA detection were described and there is evidence that the assays identify different antibodies with different prognostic value. The results of a multicenter study on four different routine tests for anti-dsDNA antibody detection showed that: (i) Farr assay displays the best diagnostic specificity/sensitivity for SLE, followed by Crithidia luciliae method (CLIFT), (ii) the new generation of solid phase assay (EliA) shows an increased sensibility versus the classical enzyme linked immune assay (ELISA) but a decreased specificity. Antibody titre detected by EliA and Farr assay correlated with disease activity. These findings would suggest that more than one assay should be useful for SLE diagnosis and monitoring. © 2005 Taylor & Francis Ltd

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The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors

Recently, the induction of SLE in naive mice employing monoclonal anti-DNA antibodies (anti-DNA Ab) carrying the pathogenic idiotype 16/6 (16/6 Id) has been reported. In the current study we report on the induction of experimental SLE by polyclonal IgG anti-DNA Ab derived from a patient with active SLE and carrying the 16/6 Id. Two different experiments were conducted in which BALB/c mice were immunized in the footpads with 1 microgram/ml or 5 micrograms/ml of anti-DNA Ab. The first experiment showed the appearance in the immunized mice of high titre anti-DNA Ab together with antinuclear antibodies, alopecia and proteinuria. In the second experiment we compared, as immunizing agents, 16/6 positive anti-DNA Ab and 16/6 negative anti-tetanus toxoid antibodies (anti-TT Ab) obtained from the serum of the same patients. Our results show that only mice immunized with 16/6 positive antibodies produced anti-DNA Ab, while mice immunized with anti-TT Ab did not show any DNA-binding activity but, surprisingly, developed high titre anti-cardiolipin antibodies