Chasing the Zebra: a case of membranous-like Glomerulopathy with SSA/RO52 deposits and no overt connective tissue disease.

BACKGROUND: The nature of the deposits in immune-mediated glomerulonephritis with a membranous pattern and masked IgG-Kappa deposits (MGMID) remains still to be elucidated. CASE PRESENTATION: We present a case of 33-year-old woman developing a continuous asymptomatic proteinuria (0.8-1 g/24 h) with no overt connective tissue diseases. She tested positive at high titers for SSA antibodies (Ro52 838 UI/mL, Ro60 2716 UI/mL) and at the kidney biopsy histological findings were compatible with an immune-mediated glomerulonephritis with a membranous pattern and masked IgG-Kappa deposits. Also, we demonstrated a positive immunohistochemistry staining for anti-Ro52-SSA antibodies, with a granular positivity in mesangium and along rare glomerular capillaries. To date, only one case of a patient with overt diagnosis of Sjögren's syndrome with MGMID has been described but a pathogenic role for SSA and SSB antibodies has never been proven. CONCLUSIONS: In this case, we described for the first time by immunohistochemistry a Ro52+ granular positivity in the mesangium and glomerular capillaries, potentially paving the way for a better understanding of MGMID.

Finding the Needle in the Haystack: Serological and Urinary Biomarkers in Behçet's Disease: A Systematic Review.

Urinary and serological markers play an essential role in the diagnostic process of autoimmune diseases. However, to date, specific and reliable biomarkers for diagnosing Behçet's disease (BD) are still lacking, negatively affecting the management of these patients. To analyze the currently available literature on serological and urinary BD biomarkers investigated in the last 25 years, we performed a systematic literature review using the Population, Intervention, Comparison, and Outcomes (PICO) strategy. One hundred eleven studies met the eligibility criteria (6301 BD patients, 5163 controls). Most of them were retrospective, while five (5%) were prospective. One hundred ten studies (99%) investigated serological biomarkers and only two (2%) focused on urinary biomarkers. One hundred three studies (93%) explored the diagnostic potential of the biomolecules, whereas sixty-two (56%) tested their effect on disease activity monitoring. Most articles reported an increase in inflammatory markers and pro-oxidant molecules, with a decrease in antioxidants. Promising results have been shown by the omics sciences, offering a more holistic approach. Despite the vast number of investigated markers, existing evidence indicates a persistent gap in BD diagnostic/prognostic indices. While new steps have been taken in the direction of pathogenesis and disease monitoring, international efforts for the search of a diagnostic marker for BD are still needed.

The Impact of Anti-SARS-CoV-2 Vaccine in Patients with Systemic Lupus Erythematosus: A Multicentre Cohort Study.

Vulnerable subjects, including systemic lupus erythematosus (SLE) patients, have been prioritised to receive anti-SARS-CoV-2 vaccines. Few data about the safety of these vaccines in SLE are available. The aim of our study is to investigate the safety of anti-SARS-CoV-2 vaccines in SLE. We included 452 SLE patients, referring to seven tertiary centres, who were immunised. A total of 119 (26%) reported side effects (SE) after the first and/or the second shot (the most frequent SE were fever, local reaction, fatigue, and arthralgia). Patients with constitutional symptoms and those on an immunosuppressive regimen (especially belimumab) showed more SE. In addition, 19 (4%) had a flare after the immunisation (flares classified by organ involvement: six musculoskeletal with constitutional symptoms, four renal, three cardio-respiratory, three haematological, two mucocutaneous). None of the patients needed hospitalisation and none died. Moreover, 15 required a transient increase in corticosteroids and four were treated with steroid pulses. One patient required an additional rituximab course. Anti-dsDNA, moderate/high DAS before vaccine, and belimumab were found more frequently in patients with disease flare. Anti-SARS-CoV-2 vaccines are safe in SLE patients, and they should be recommended in these patients, as the potential benefits widely outweigh the risk of SE. Treatment adjustment might be considered with the aim of minimising SE risk and flare.

Clinical and peculiar immunological manifestations of SARS-CoV-2 infection in systemic lupus erythematosus patients.

OBJECTIVES: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with SLE remains unclear and data on clinical manifestations after infection are lacking. The aim of this multicentre study is to describe the effect of SARS-CoV-2 in SLE patients. METHODS: SLE patients referring to four Italian centres were monitored between February 2020 and March 2021. All patients with SARS-CoV-2 infection were included. Disease characteristics, treatment, disease activity and SARS-CoV-2-related symptoms were recorded before and after the infection. RESULTS: Fifty-one (6.14%) SLE patients were included among 830 who were regularly followed up. Nine (17.6%) had an asymptomatic infection and 5 (9.8%) out of 42 (82.6%) symptomatic patients developed interstitial pneumonia (no identified risk factor). The presence of SLE major organ involvement (particularly renal involvement) was associated with asymptomatic SARS-CoV-2 infection (P = 0.02). Chronic corticosteroid therapy was found to be associated with asymptomatic infection (P = 0.018). Three SLE flares (5.9%) were developed after SARS-CoV-2 infection: one of them was characterized by MPO-ANCA-positive pauci-immune crescentic necrotizing glomerulonephritis and granulomatous pneumonia. CONCLUSIONS: SARS-CoV-2 infection determined autoimmune flares in a small number of patients. Our data seem to confirm that there was not an increased risk of SARS-CoV-2 in SLE. Patients with asymptomatic SARS-CoV-2 infections were those having major SLE organ involvement. This may be explained by the high doses of corticosteroids and immunosuppressive agents used for SLE treatment.

Prognostic and Diagnostic Values of Novel Serum and Urine Biomarkers in Lupus Nephritis: A Systematic Review.

INTRODUCTION: While renal biopsy remains the gold standard for diagnosing lupus nephritis (LN), the prognostic and diagnostic role of non-invasive biomarkers for LN is currently debated. METHODS: Available studies published in last 5 years (2015-2020) assessing the diagnostic and prognostic value of urinary and/or serological biomarkers in subjects with LN were analyzed in this systematic review. RESULTS: Eighty-five studies were included (comprehending 13,496 patients with systemic lupus erythematosus [SLE], 8,872 LN, 487 pediatric LN, 3,977 SLE but no LN, 160 pediatric SLE but no LN and 7,679 controls). Most of the studies were cross-sectional (62; 73%), while 14 (17%) were prospective. In sixty studies (71%), the diagnosis of LN was biopsy-confirmed. Forty-four out of 85 (52%) investigated only serological biomarkers, 29 studies (34%) tested their population only with urinary biomarkers, and 12 (14%) investigated the presence of both. Outcome measures to assess the clinical utility of the analyzed biomarkers were heterogeneous, including up to 21 different activity scores, with the SLEDAI (in 60%) being the most used. Despite some heterogeneity, promising results have been shown for biomarkers such as urinary monocyte chemoattractant protein, urinary adiponectin, and urinary vascular cell adhesion protein 1. DISCUSSION/CONCLUSION: While serum and urine biomarkers have the potential to improve diagnostic and prognostic pathways in patients with LN, the vast heterogeneity across studies severely limits their applicability in current clinical practice. With the kidney biopsy still representing the gold standard, future efforts should focus on harmonizing study inclusion criteria and outcomes, particularly in clinical trials, in order to improve comparability and facilitate the implementations of available biomarkers into the daily practice.

Anti-beta-2-glycoprotein I domain 1 identifies antiphospholipid antibodies-related injuries in patients with concomitant lupus nephritis.

BACKGROUND: In this study we aimed to evaluate the usefulness of domain profiling of Beta-2-glycoprotein I(ß2GPI)-Domain-1 (D1) antibodies in relation to antiphospholipid antibodies (aPL)-related nephropathy (aPL-N) in patients with biopsy-proven lupus nephritis (LN). METHODS: Of 124 consecutive patients (96 women, mean age 45.5 ± 12.3 years, mean disease duration 14.7 ± 9.6 years) fulfilling the 1982 criteria for systemic lupus erythematosus (SLE), we identified 39 patients (mean age 39.84 ± 8.6 years, mean disease duration 11.3 ± 7.7 years) with the following characteristics: (a) biopsy-proven LN; (b) no previous diagnosis of antiphospholipid syndrome (APS) according to the current classification criteria. RESULTS: Patients with both LN and aPL-N had higher median aß2GPI-D1 antibody titres (220.1 CU, 25-75th IQ 29.1-334.2) as compared those with LN alone (46.5 CU, 25-75th IQ 12.5-75.1) (p = 0.0087). Median aß2GPI-D1 antibody titres were higher in patients with acute thrombotic microangiopathy (aTMA) (N = 7) (250.1 CU, 25-75th IQ 61.2-334.2) vs. with LN alone (46.5 CU, 25-75th IQ 12.5-75.1 CU) (p = 0.0009). Having a Global Antiphospholipid Syndrome Score > 10 confers an increased probability of having acute features of aTMA (OR 6.25, 95%CI 1.2-31.8). As compared to other aPL, aß2GPI-D1 antibodies have the best diagnostic accuracy for aTMA as evaluated by performances in Area Under the Curves in a ROC analysis. CONCLUSIONS: aß2GPI-D1 antibodies detection might provide a second-line assay to be performed in aß2GPI positive patients with LN, allowing more accurate stratification of the renal vascular involvement risk, thus potentially leading to a more tailored management.