Kidney involvement in systemic lupus erythematosus: From the patient assessment to a tailored treatment.

In the last few years, several studies have provided new evidence for the diagnosis, management, and follow-up of patients with lupus nephritis. Evidence showing dissociation between clinical and histological findings has prompted reevaluation of the role of the kidney biopsy as a tool for diagnosis and follow-up. In therapeutics, four immunosuppressive schemes now have supporting evidence for use as initial therapy.

Glomerulonephritis and autoimmune vasculitis are independent of P2RX7 but may depend on alternative inflammasome pathways.

P2RX7, an ionotropic receptor for extracellular adenosine triphosphate (ATP), is expressed on immune cells, including macrophages, monocytes, and dendritic cells and is upregulated on nonimmune cells following injury. P2RX7 plays a role in many biological processes, including production of proinflammatory cytokines such as interleukin (IL)-1β via the canonical inflammasome pathway. P2RX7 has been shown to be important in inflammation and fibrosis and may also play a role in autoimmunity.

Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization.

Antibody mediated rejection is a major cause of renal allograft loss. Circulating preformed donor specific antibodies (DSA) can result as a consequence of blood transfusion, pregnancy or prior transplantation. Current treatment strategies are limited due to partial or transient efficacy, adverse side-effects or patient unsuitability.

COVID-19 in patients with glomerular disease.

Purpose Of Review: Managing patients with glomerular disease during the COVID-19 pandemic has been challenging, as the infection risk associated with immunosuppression must be balanced against the need to control severe glomerular disease that can lead to kidney failure. This review provides an overview of COVID-19 and the effectiveness of SARS-CoV-2 vaccination in patients with glomerular disease.

Recent Findings: Registry data, although biased towards outcomes of hospitalized patients, suggest that the mortality from COVID-19 is higher in patients with glomerular disease than in the general population.

Characterisation of an enhanced preclinical model of experimental MPO-ANCA autoimmune vasculitis.

Experimental autoimmune vasculitis (EAV) is a model of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) induced by immunisation of susceptible rat strains with myeloperoxidase (MPO). Animals develop circulating MPO-ANCA, pulmonary haemorrhage, and glomerulonephritis, although renal injury is mild and recovers spontaneously without treatment. In this study we aimed to augment the severity of glomerulonephritis.

Selective Interleukin-6 Trans-Signaling Blockade Is More Effective Than Panantagonism in Reperfused Myocardial Infarction.

Interleukin (IL)-6 is an emerging therapeutic target in myocardial infarction (MI). IL-6 has 2 distinct signaling pathways: trans-signaling, which mediates inflammation, and classic signaling, which also has anti-inflammatory effects. The novel recombinant fusion protein sgp130Fc achieves exclusive trans-signaling blockade, whereas anti-IL-6 antibodies (Abs) result in panantagonism.

Live Imaging of Monocyte Subsets in Immune Complex-Mediated Glomerulonephritis Reveals Distinct Phenotypes and Effector Functions.

Background: Immune complexes within glomerular capillary walls cause crescentic GN (CrGN). Monocytes and macrophages are important in mediating CrGN, but little work has been done to phenotype the subpopulations involved and determine their respective contributions to glomerular inflammation.

Methods: Live glomerular imaging using confocal microscopy monitored intravascular monocyte subset behavior during nephrotoxic nephritis (NTN) in a novel WKY-hCD68-GFP monocyte/macrophage reporter rat strain.

Mycophenolate mofetil and tacrolimus versus tacrolimus alone for the treatment of idiopathic membranous glomerulonephritis: a randomised controlled trial.

Background: Tacrolimus (TAC) is effective in treating membranous nephropathy (MN); however relapses are frequent after treatment cessation. We conducted a randomised controlled trial to examine whether the addition of mycophenolate mofetil (MMF) to TAC would reduce relapse rate.

Methods: Forty patients with biopsy proven idiopathic MN and nephrotic syndrome were randomly assigned to receive either TAC monotherapy (n = 20) or TAC combined with MMF (n = 20) for 12 months.

Positive antineutrophil cytoplasmic antibody serology in patients with lupus nephritis is associated with distinct histopathologic features on renal biopsy.

Class IV-S lupus nephritis is often associated with more necrosis and fewer subendothelial immune deposits compared to class IV-G lupus nephritis, suggestive of necrotising glomerular inflammation found in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. ANCAs are present in a significant proportion of patients with lupus nephritis. Here we determine whether ANCAs are associated with distinct clinical and histopathologic features of lupus nephritis.

Clinical characteristics and outcomes of HIV-associated immune complex kidney disease.

Background: The pathogenesis and natural history of HIV-associated immune complex kidney disease (HIVICK) is not well understood. Key questions remain unanswered, including the role of HIV infection and replication in disease development and the efficacy of antiretroviral therapy (ART) in the prevention and treatment of disease.

Methods: In this multicentre study, we describe the renal pathology of HIVICK and compare the clinical characteristics of patients with HIVICK with those with IgA nephropathy and HIV-associated nephropathy (HIVAN).

Induction treatment of ANCA-associated vasculitis with a single dose of rituximab.

Objectives: Rituximab is effective in inducing remission in ANCA-associated vasculitis (AAV), with randomized evidence to support its use as four infusions of 375 mg/m(2) (the conventional lymphoma dosing schedule). As B cell depletion (BCD) appears to occur very rapidly after the first dose, we questioned the need for repeat dosing and adopted a standard single-dose protocol of 375 mg/m(2) to treat active AAV.

Methods: All consecutive cases with newly diagnosed or relapsing AAV for whom conventional immunosuppression was contraindicated or ineffective were enrolled.

B-cell numbers and phenotype at clinical relapse following rituximab therapy differ in SLE patients according to anti-dsDNA antibody levels.

Objectives: To correlate the kinetics of B-cell repopulation with relapse after B-cell depletion therapy in SLE patients and address whether variation in relapse rate, B-cell numbers and phenotype are related to anti-dsDNA antibody levels.

Methods: Sixty-one patients with refractory SLE were treated with a standard rituximab regimen. Clinical and serological measures of disease activity and B-cell numbers were assessed.

Interactions of human monoclonal and polyclonal antiphospholipid antibodies with serine proteases involved in hemostasis.

Objective: To characterize the interaction between procoagulant and/or anticoagulant serine proteases and human monoclonal IgG antiphospholipid antibodies (aPL) and polyclonal IgG derived from patients with the antiphospholipid syndrome (APS).

Methods: Five human monoclonal IgG with small differences in their sequences were tested for binding to protein C, activated protein C, plasmin, factor VIIa (FVIIa), FIX, FIXa, and FXII. Serum levels of antithrombin and anti-activated protein C were compared in 32 patients with APS, 29 patients with systemic lupus erythematosus (SLE), and 22 healthy controls.

The efficacy of repeated treatment with B-cell depletion therapy in systemic lupus erythematosus: an evaluation.

Objective: Since 2000, we have given B-cell depletion therapy (BCDT) with rituximab to 76 patients with active SLE refractory to standard immunosuppression. Twenty-four of these patients have now received repeated cycles of BCDT. The aims of the study were to: (i) assess the efficacy and safety of repeated cycles of BCDT in treating refractory SLE; and (ii) assess whether retreatment produced a more sustained clinical response.

Development and initial validation of a self-assessed lupus organ damage instrument.

Objective: The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) is a validated instrument for assessing organ damage in systemic lupus erythematosus (SLE). Trained physicians must complete it, thus limiting utility where this is impossible.

Methods: We developed and pilot tested a self-assessed organ damage instrument, the Lupus Damage Index Questionnaire (LDIQ), in 37 SLE subjects and 7 physicians.

Diagnosis and treatment of depression following acquired brain injury: a comparison of practice in the UK and the Netherlands.

Objective: To describe and compare current practice in diagnosis and treatment of depression following acquired brain injury in two countries (UK and the Netherlands) which have different sets of guidelines.

Setting And Design: A cross-sectional survey of reported practice among rehabilitation physician members of the British and Dutch specialist societies.

Methods: A 12-item postal questionnaire was sent to 496 rehabilitation physicians with two reminders: N=353 (71%) responded, 146 of whom did not manage people with acquired brain injury, leaving 207 questionnaires for analysis (Netherlands N=121, UK N=86).

Interactions between nitric oxide and corticosterone in the regulation of progenitor cell proliferation in the dentate gyrus of the adult rat.

It is well established that L-NAME, a generic NOS inhibitor, stimulates neurogenesis in the dentate gyrus of the adult rat and corticosterone reduces it. These experiments explore the interaction between L-NAME and corticosterone. L-NAME (50 mg/kg), as expected, increased proliferation, but also lowered plasma corticosterone levels.