Lupus-like Glomerulonephritis Research Articles

Blood platelets in chronic graft-versus-host disease: association with Th1/Th2 ratio

As found in clinical and laboratory studies, platelets not only play a key role in the processes of coagulation and thrombosis, but are also able to actively participate in other pathophysiological processes, including the development of immune reactions. It has been shown that changes in the immune system leading to systemic lupus erythematosus (SLE) are often accompanied by changes in the number of platelets and their activity in the peripheral blood of SLE patients, which correlate with the severity of the clinical manifestations of the disease. Earlier we have studied the standard experimental model of SLE in detail, based on the induction of chronic graft-versus-host disease (cGVHD) in the semi-allogeneic system DBA/2 → (C57Bl/6 x DBA/2)F1. However, the participation of platelets in this immunopathological process has not been studied. There are no data in the literature on the behavior of platelets in cGVHD or on their relationship with the state of Th1/Th2 balance. It can been expected that the platelet count changes according to the development of cGVHD in the used experimental model by analogy with the development of SLE in humans.In the experiments, we used female mice of the DBA/2 strain and (C57Bl/6 × DBA/2)F1 hybrids. Chronic GVHD in a semi-allogeneic system was induced by injecting DBA/2 mouse splenocytes into B6D2F1 hybrid mice: 60-70 × 106 cells intravenously twice with an interval of 6 days. The studied parameters were evaluated three months after the start of the experiment and the formation of lupus-like glomerulonephritis in animals with Th2-dependent cGVHD variant.A decrease in the number of erythrocytes and hemoglobin, a decrease in hematocrit and a parallel increase in the number of reticulocytes in the blood of mice with cGVHD are in good agreement with our earlier conclusion that these animals have autoimmune hemolytic anemia. It was found that, platelets increase significantly with the development of cGVHD unlike other blood cells. Secondary thrombocytosis is observed in the case of the Th2-dependent variant of сGVHD in this model of SLE, while in the group with the Th1-dependent variant of сGVHD, the average number of platelets in the blood does not differ from the control group.

Development of a novel Poly (I:C)-induced murine model with accelerated lupus nephritis and examination of the therapeutic effects of mycophenolate mofetil and a cathepsin S inhibitor

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multi-organ systems with a widely heterogeneous clinical presentation. Renal involvement, observed mainly in lupus nephritis (LN), is the most common organ lesion associated with SLE and a determinant of prognosis. However, treatment of LN remains controversial and challenging, prompting the need for novel therapeutic approaches. In particular, development of a clinically relevant LN animal model would greatly facilitate the development of new treatments. Here, we report a novel murine model for LN established by administering polyinosinic-polycytidylic acid (Poly (I:C)) to NZB/W F1 mice. We investigated the effectiveness of administering Poly (I:C) to NZB/W F1 mice for accelerating nephritis onset and explored the optimal conditions under which to enroll mice with nephritis with similar pathology for studying treatment candidates. Gene-expression analysis revealed that activation of macrophages, which are reported to be involved in the progression of LN in patients, was a unique characteristic in this accelerated nephritis model. Evaluation of the therapeutic effect of mycophenolate mofetil (MMF), a recommended first-choice agent for LN, in this novel LN model showed that MMF significantly reduced proteinuria. The cathepsin S (CatS) inhibitor ASP1617, which has been reported to prevent development of lupus-like glomerulonephritis in the spontaneous NZB/W F1 mouse model, also showed marked therapeutic effect in this model. Our novel Poly (I:C) accelerated LN model would thus be very useful for screening clinical candidates for LN, and CatS may be an attractive therapeutic target for the treatment of LN.

Potential benefit of the cathepsin S inhibitor, ASP1617, as a treatment for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the dysregulation of various cell types and immunological pathways. Autoantibodies play an important role in its pathogenesis. The presence of autoantibodies suggests that self-antigen presentation through major histocompatibility complex (MHC) class II on antigen presenting cells is involved in the pathogenesis of autoimmune diseases, including SLE. Cathepsin S (CatS) is a key protease for antigen peptide loading onto lysosomal/endosomal MHC class II molecules through invariant chain degradation to promote antigen presentation. Inhibition of CatS is therefore expected to suppress antigen presentation via MHC class II, T and B cell activation, and antibody production from B cells. Here, we report the pharmacological profile of ASP1617, a novel CatS inhibitor. ASP1617 induced invariant chain accumulation and decreased the expression level of MHC class ΙΙ on the cell surface in both mouse and human B cells. Further, ASP1617 prevented DO11.10 mice T cell proliferation to ovalbumin antigen. We investigated the effects of ASP1617 and mycophenolate mofetil (MMF) on the development of lupus-like nephritis in NZB/W F1 mice, a widely used SLE mouse model. Oral administration of ASP1617 suppressed anti-dsDNA IgG, prevented progression of lupus-like glomerulonephritis, and significantly prevented proteinuria excretion. In contrast, MMF did not suppress anti-dsDNA IgG. Further, we found that plasma and/or urine CatS levels were increased in specimens from NZB/W F1 mice and several SLE patients. These results indicate that CatS may be an attractive therapeutic target for the treatment of SLE.

A Diverse Spectrum of Immune Complex– and Complement-Mediated Kidney Diseases Is Associated With Mantle Cell Lymphoma

IntroductionThere are limited reports on kidney biopsy findings in patients with mantle cell lymphoma (MCL).MethodsWe initiated a multi-institutional, retrospective review of kidney biopsy findings in patients with active and treated MCL.ResultsA total of 30 patients with MCL and kidney biopsies were identified, with a median age of 67 (range 48–87) years, 73% of whom were men. A total of 20 patients had active MCL at the time of biopsy, of whom 14 (70%) presented with acute kidney injury (AKI), proteinuria and/or hematuria, and biopsy findings potentially attributable to lymphoma. Of the 14, 11 had immune complex (IC) or complement-mediated (C3) disease including proliferative glomerulonephritis (GN) with monotypic Ig deposits (PGNMID [2]), C3GN, (2), secondary membranous nephropathy (MN [3]), tubular basement membrane (TBM) deposits (2), and modest lupus-like GN (2). Lymphomatous infiltration was present in 8 of the 20 patients, 5 with coincident IC or C3 lesions. A total of 6 patients with available follow-up were treated for MCL, all with clinical remission of GN (2 PGNMID, 2 C3GN, and 2 MN).ConclusionMCL is associated with diverse monoclonal and polyclonal glomerular and extra-glomerular IC and C3 disease. For patients with active MCL and kidney dysfunction requiring biopsy, 70% had findings due or potentially due to lymphoma, including 55% with IC or C3 disease and 40% had lymphomatous kidney infiltration. IC and C3GN in the setting of active MCL was responsive to lymphoma-directed therapy.

De novo lupus-like glomerulonephritis after pediatric non-kidney organ transplantation

BackgroundWe propose a novel clinically significant finding, de novo lupus-like glomerulonephritis (DNLLGN), in patients with autoantibodies and kidney abnormalities in pediatric liver transplant (LT) and intestinal inclusive transplants (ITx).MethodsWe describe the clinical, serologic, and histopathologic presentation and kidney outcomes in eight patients from our center found to have DNLLGN on kidney biopsy.ResultsPediatric recipients of non-kidney solid organ transplants developed an unusual de novo immune complex glomerulonephritis with morphologic similarity to lupus nephritis. Six had isolated LT (0.9% of all pediatric LT at our center) and two had ITx (2.1% of all ITx). Five (63%) presented with nephrotic syndrome. Five patients had autoantibodies. Patients underwent kidney biopsy at a mean of 11.5 years in LT and 2.8 years in ITx after the index transplant. Biopsies demonstrated changes similar to focal or diffuse active lupus. Follow-up eGFR at a mean of 6 years after biopsy showed a mean decrease of 30 ml/min/1.73 m2 in all patients (p = 0.11).ConclusionsDNLLGN has not been previously recognized in this clinical setting, yet 8 kidney biopsies from pediatric recipients of LT and ITx at our center in 25 years demonstrated this finding. DNLLGN appears to be an under-reported phenomenon of clinical significance.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information.

Systemic Lupus Erythematosus and Virus C Infection - Diagnosis, Evolution and Treatment Particularities

Abstract Lupus erythematosus (SLE) is an autoimmune disease with a broad spectrum of clinical and immunologic manifestations. Hepatitis C virus (HCV) has been postulated as a potential etiologic or triggering agent among other viruses and it appears to be associated with the presence of autoimmune disorders, even mimicking SLE clinically and serologically. Data on the association between HCV infection and SLE are scarce, but an interaction between these two conditions seems possible. As for treatment options, it is well known that the classic antiviral therapy with interferon may aggravate preexisting autoimmunity, unmask previously silent autoimmune processes, or even cause the emergence of de novo autoimmune disease, including SLE. Interferon-free treatment seems to be more efficacious, safer and more tolerable. However, it is important that clinicians be aware that DAAs (direct acting antivirals) can also trigger lupus-like immune complex-mediated glomerulonephritis. There is scant data on the use of immunosuppressive drug therapy in HCV patients. It seems that enhanced HCV replication due to immunosuppression does not lead to clinically significant sequelae and growing evidence has been reported that supports its efficacy and safety. Patients with SLE and virus C infection are a special category, a fact that the clinician needs to take in consideration in order to a better approach, all the more as these patients are at increased risk for developing end-stage renal disease and have a lower survival rate than general population.

Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy

BackgroundThe seroprevalence of human Parvovirus B19 (PVB19) is 70–85% in adults worldwide. PVB19 is the etiologic agent of the fifth disease, is a cause of aplastic anemia, and can be associated with kidney injury. We aimed to describe the cases of 4 patients with kidney injury related to PVB19 primary infection, and to evaluate the seroprevalence of PVB19 and the incidence of PVB19 primary infection in patients undergoing a native kidney biopsy.MethodsCases of PVB19 infection with kidney injury were reviewed from the archives of the department of Nephrology. A systematic screening of anti-PVB19 IgG and IgM antibodies and viral DNA was performed in sera from 100 consecutive patients with a kidney biopsy in 2017–2018.ResultsThe 4 patients with PVB19 infection-associated kidney disease displayed: one lupus-like glomerulonephritis (GN) without lupus auto-antibodies, one minimal change disease with tubular necrosis, one secondary hemolytic and uremic syndrome and one membrano-proliferative GN. In the 100 patients biopsied, 67 had elevated anti-PVB19 IgG, among whom 8 had elevated IgM, without circulating viral DNA, without any particular renal pathological pattern. One additional patient showed a seroconversion at the time of kidney biopsy, which revealed a class V lupus nephritis.ConclusionPVB19 primary infection can be associated with different kidney diseases. The seroprevalence of PVB19 among patients with a kidney biopsy is similar to the overall population, and primary infection is rarely documented (1%) after systematic screening. Whether PV19 is nephrotoxic, or triggers renal endothelial injury and immune activation, remains to be elucidated.

SAT-411 Anti nuclear Antibody negative Lupus like Nephritis. A 5 case series report

Systemic lupus erythematosus (SLE) is a disease due to an autoantibody response to nuclear and cytoplasmic antigen which is associated with the inflammatory cascades and end-organ damage in multiple organs like kidney, skin, brain, etc. In the kidney, immune-complex deposits leads to the deterioration of renal function leading to a condition called lupus nephritis. Lupus nephritis is a common but serious complication in SLE patients. Previously, American College of Rheumatology (ACR) required at least 4 of 11 clinical or laboratory criteria to diagnose SLE which included malar rash, discoid rash, photosensitivity, oral ulcers, nonerosive arthritis, pleuritis or pericarditis, kidney disorder, neurological disorder, hematologic disorder and positive antinuclear antibody. In 2019, there has been an update in this criteria, where positive antinuclear antibody is given as entry level criterion. If negative, cases cannot be classified as Systemic lupus erythematosus. If positive, further accumulation of 10 points is required for diagnosis of SLE. Lupus-like glomerulonephritis is defined as immune complex kidney disease with full house pattern in glomeruli where immunofluorescence staining for immunoglobulin G (IgG), IgA, IgM, complement (C3), and C1q are positive in an ANA negative patients. This findings is otherwise described as diagnostic criteria for lupus nephritis in SLE patients. Extraglomerular immune deposits within tubular basement membranes and tubuloreticular inclusions are other characteristic features that can be found in lupus nephritis. A total of 5 cases of ANA negative lupus like nephritis were reported in the department of renal pathology in University of Alberta between 1st January 2019 to 30th September, 2019. All of our cases were positive (IgG, IgA, IgM, C3, C1q) in immunofluorescence and were described as full house pattern. In light microscopy, 2 of the cases correlated with stage IV lupus nephritis, 2 correlated with stage V lupus nephritis and 1 case correlated with stage I lupus nephritis. Tubuloreticular inclusions were present in the one of the case. All patients responded to prednisolone as suggested by follow up laboratory datas.Table 1Variations in parameters among five cases.Case 1Case 2Case 3Case 4Case 5Age/sex62y/f56y/f24y/m42y/m7y/fANANegativeNegativeNegativeNegativeNegativedsDNANegative (positive after 2 month borderline 127 <120MFU)NegativeNegativeNegativeNegativeProtein creatinine ratio (PCR)306.3553.9(Normal <13.0 mg/mmol)238.57439.33975.52Urine Hemoglobin2+1+3+1+1+Serum. Creatinine121 (40-100 µmol/L)84 (40-100 µmol/L)106 (50-120 µmol/L)146 (50-120 µmol/L)29 (20-75 µmol/L)HematologyNormalNormalNormalNormalNormalLupus Nephritis gradeIVIIVVV Open table in a new tab In ANA negative patients, immune complex mediated glomerulonephritis with full house immunofluorescence pattern may be considered as lupus like glomerulonephritis. Other features like tubuloreticular inclusions, DsDNA might be positive in these patients. These patients present and response to treatment like renal limited lupus nephritis. They may develop full blown SLE in long term; hence close follow up is required. However, other causes of immune complex mediated glomerulonephritis must be ruled out before considering this diagnosis.

Gαq deficiency accelerates the onset of experimental lupus

Abstract Systemic lupus erythematosus is related to abnormal expression of type I interferon signature genes and characterized by a variety of clinical manifestations and autoantibody production. Tetramethylpentadecane (TMPD), also called as pristine, induced a murine model of systemic lupus erythematosus. Taking pristine to genetically normal mice results in the production of lupus-like autoantibodies and glomerulonephritis, similar to human lupus nephritis. Our previous studies have shown a crucial role of Gαq in immune system. In this study, we treated Gnaq+/− mice with pristane using C57BL/6 mice as controls. Gnaq+/− mice developed antinuclear antibodies earlier than the control mice; also, their titers were higher than the controls. pDCs were increased in the peritoneal lavage fluid of Gnaq+/− mice injected for 7 days compared to controls. Th1 and Th17 cells both were increased significantly in injected Gnaq+/− mice after a month. Gnaq+/− mice took place into more severe kidney damage than controls. Together all, our findings demonstrate that Gαq deficiency accelerated lupus occurrence.

Patrolling monocytes promote the pathogenesis of early lupus-like glomerulonephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with genetic and environmental contributions. Hallmarks of the disease are the appearance of immune complexes (IC) containing autoreactive Abs and TLR-activating nucleic acids, whose deposition in kidney glomeruli is suspected to promote tissue injury and glomerulonephritis (GN). Here, using a mouse model based on the human SLE susceptibility locus TNFAIP3-interacting protein 1 (TNIP1, also known as ABIN1), we investigated the pathogenesis of GN. We found that GN was driven by TLRs but, remarkably, proceeded independently of ICs. Rather, disease in 3 different mouse models and patients with SLE was characterized by glomerular accumulation of patrolling monocytes (PMos), a cell type with an emerging key function in vascular inflammation. Consistent with such function in GN, monocyte-specific deletion of ABIN1 promoted kidney disease, whereas selective elimination of PMos provided protection. In contrast to GN, PMo elimination did not protect from reduced survival or disease symptoms such as IC generation and splenomegaly, suggesting that GN and other inflammatory processes are governed by distinct pathogenic mechanisms. These data identify TLR-activated PMos as the principal component of an intravascular process that contributes to glomerular inflammation and kidney injury.

Essential Roles for Mannose-Binding Lectin-Associated Serine Protease-1/3 in the Development of Lupus-Like Glomerulonephritis in MRL/lpr Mice.

The complement system, composed of the three activation pathways, has both protective and pathogenic roles in the development of systemic lupus erythematosus (or lupus), a prototypic autoimmune disease. The classical pathway contributes to the clearance of immune complexes (ICs) and apoptotic cells, whereas the alternative pathway (AP) exacerbates renal inflammation. The role of the lectin pathway (LP) in lupus has remained largely unknown. Mannose-binding lectin (MBL)-associated serine proteases (MASPs), which are associated with humoral pattern recognition molecules (MBL or ficolins), are the enzymatic constituents of the LP and AP. MASP-1 encoded by the Masp1 gene significantly contributes to the activation of the LP. After the binding of MBL/ficolins to pathogens or self-altered cells, MASP-1 autoactivates first, then activates MASP-2, and both participate in the formation of the LP C3 convertase C4b2a, whereas, MASP-3, the splice variant of the Masp1 gene, is required for the activation of the zymogen of factor D (FD), and finally participates in the formation of the AP C3 convertase C3bBb. To investigate the roles of MASP-1 and MASP-3 in lupus, we generated Masp1 gene knockout lupus-prone MRL/lpr mice (Masp1/3−/− MRL/lpr mice), lacking both MASP-1 and MASP-3, and analyzed their renal disease. As expected, sera from Masp1/3−/− MRL/lpr mice had no or markedly reduced activation of the LP and AP with zymogen forms of complement FD. Compared to their wild-type littermates, the Masp1/3−/− MRL/lpr mice had maintained serum C3 levels, little-to-no albuminuria, as well as significantly reduced glomerular C3 deposition levels and glomerular pathological score. On the other hand, there were no significant differences in the levels of serum anti-dsDNA antibody, circulating ICs, glomerular IgG and MBL/ficolins deposition, renal interstitial pathological score, urea nitrogen, and mortality between the wild-type and Masp1/3−/− MRL/lpr mice. Our data indicate that MASP-1/3 plays essential roles in the development of lupus-like glomerulonephritis in MRL/lpr mice, most likely via activation of the LP and/or AP.

Mouse models for immunology research available from The Jackson Laboratory Repository.

Abstract The Jackson Laboratory Repository serves as a centralized facility for the development, distribution and cryopreservation of mouse models of human biology and disease. Hundreds of new strains are added annually to one of the largest collections of characterized mouse strains available. This poster presents our newest strains involving genes associated with adaptive immunity. The Pdcdl (programmed cell death 1 - PD1) knockout (KO) mice allow increased infiltration of inflammatory cells in several disease models. CC10-OVA transgenic mice direct OVA expression to lung epithelium; and a KO/KI mouse expresses tamoxifen-inducible cre under the control of the Cd19 promoter in B lymphocytes. New mouse models with mutations in genes involved in the innate immune response include: Dectin-1 (Clec7a) KO mice, which exhibit increased sensitivity to fungal infection and a dysregulated chemokine response; GM-CSF (Csf2) KO mice with impaired phagocytosis, a lupus-like disorder and glomerulonephritis; mice with a KO in MPYS (Tmem173), a pattern recognition receptor that activates type 1 interferon; Ccr2gfp KI/KO mice used in tracking monocyte chemotaxis; a transgenic mouse model of hyperimmunoglobulin E syndrome that expresses modified Stat3; and a new addition to our extensive collection of interleukin mutants, Il1a, a new conditional KO/reporter allele that is produced by monocytes and macrophages. Additionally, several Cas9-expressing lines, requiring only a specific single guide RNA to generate single or multiple simultaneous mutations, are available. These lines overcome the burden of packaging size limits. Researchers are encouraged to deposit mice to the Repository: www.jax.org/donate-a-mouse.

An unusual case of glomerulonephritis in a patient with non-Hodgkin Mucosal Associated Lymphoid Tissue (MALT) B-cell lymphoma

BackgroundKidney involvement in non-Hodgkin lymphoma is well recognized and glomerulonephritis, when present, has been commonly reported to be associated with a membranoproliferative pattern.Case presentationWe report a case of a 58-year-old lady with a recurrence of non-Hodgkin MALT B-cell lymphoma, presenting with acute kidney injury, nephrotic range proteinuria and a cellular urinalysis. She underwent a renal biopsy that showed a severe diffuse proliferative and exudative lupus-like glomerulonephritis, which is likely paraneoplastic in nature. We discuss the differential diagnosis and possible pathogenesis of glomerular injury in lymphoma-related proliferative glomerulonephritis.ConclusionDifferentiating between true lupus nephritis and a paraneoplastic glomerulonephritis is important, as it would have significant implications on treatment and clinical course.

Immune Complex Disease With a Lupus-like Pattern of Deposition in an Antinuclear Antibody–Negative Patient

Immune complex-mediated glomerulonephritis can be caused by a multitude of disease processes and may manifest in a variety of histologic patterns. Lupus nephritis is an immune complex disease, the diagnosis of which requires that the affected patient have systemic lupus erythematosus (SLE). In the absence of SLE, the finding of glomerulonephritis with certain patterns of immune complex deposition characteristic of lupus nephritis has been referred to as lupus-like glomerulonephritis. Immunoglobulin G (IgG), IgA, IgM, complement C3, and C1q deposition in glomerular immune deposits is one such pattern. We report a case of immune complex disease in a primarily membranous distribution with mesangial, subendothelial, and tubular basement membrane deposits with IgG, IgA, IgM, C3, and C1q deposition in a patient with proteinuria, photosensitive dermatitis, and a positive lupus anticoagulant test. The patient had 3 of the clinical criteria for SLE, thus failing to meet the diagnosis based on the American College of Rheumatology definition. In this case, a diagnosis of lupus-like glomerulonephritis was made after other causes of membranous glomerulopathy were excluded. This teaching case highlights the broad differential diagnosis of this pattern of injury and reviews similar cases in the literature.

A cardiorenal-pulmonary-cutaneous-muscle syndrome.

Anti-synthetase syndrome is a relatively recently described auto-immune disease characterized by auto-antibodies to enzymes that acetylate transfer RNA (tRNA). Interstitial pulmonary disease and inflammatory myopathy are regular findings. Our patient also exhibited a lupus-like glomerulonephritis. An important clue was the presence of ‘mechanics’ hands. Nephrologists need to be aware of this syndrome.

CD4+ Th1 cells are effectors in lupus nephritis—but what are their targets?

Lupus nephritis involves both humoral and cellular effectors. Okamoto and colleagues isolated renal CD4+ cells from lupus-prone mice, selecting cells expressing T-cell receptors on the basis of their activity. After transfecting CD4+ cells with the relevant T-cell receptors, they transferred them into mice and induced more severe glomerulonephritis. This study supports a direct role for Th1 cells in lupus nephritis, although their antigenic specificity remains uncertain, as they did not recognize nucleosomes.

Immune complex-mediated co-ligation of the BCR with FcγRIIB results in homeostatic apoptosis of B cells involving Fas signalling that is defective in the MRL/Lpr model of systemic lupus erythematosus

Negative regulation of B cell activation by cognate immune complexes plays an important homeostatic role in suppressing B cell hyperactivity and preventing consequent autoimmunity. Immune complexes co-ligate the BCR and FcγRIIB resulting in both growth arrest and apoptosis. We now show that such apoptotic signalling involves induction and activation of p53 and its target genes, the pro-apoptotic Bcl-2 family members, Bad and Bid, as well as nuclear export of p53. Collectively, these events result in destabilisation of the mitochondrial and lysosomal compartments with consequent activation and interplay of executioner caspases and endosomal-derived proteases. In addition, the upregulation of Fas and FasL with consequent activation of caspase 8-dependent death receptor signalling is required to facilitate efficient apoptosis of B cells. Consistent with this role for Fas death receptor signalling, apoptosis resulting from co-ligation of the BCR and FcγRIIB is defective in B cells from Fas-deficient MRL/MpJ-Faslpr mice. As these mice develop spontaneous, immune complex-driven lupus-like glomerulonephritis, targeting this FcγRIIB-mediated apoptotic pathway may therefore have novel therapeutic implications for systemic autoimmune disease.

Lack of IL-21R on donor cells attenuates chronic GVHD but promotes humoral autoimmunity in acute GVHD (56.11)

Abstract IL-21 enhances CD8 maturation into cytotoxic T lymphocytes (CTL), promotes the differentiation of T follicular helper cells (TFH) cells and Th17 cells, downregulates Tregulatory (Treg) cells and exerts stimulatory activities on B cells, suggesting a complex role for IL-21 in promoting autoimmunity. To assess the role of IL-21/IL-21R interaction on CD4 and CD8 T cells in promoting lupus-like disease we used the parent-into-F1 model of acute and chronic graft versus host disease (GVHD) using IL-21R KO and wild type B6 mice as donors. cGVHD induced with CD8 depleted splenocytes from IL-21R KO mice exhibited an attenuated disease phenotype characterized by significant decrease in the number of donor (d)CD4 and dTFH cells, impaired help for B cells as determined by anti-ssDNA antibody levels and less severe lupus-like glomerulonephritis. However the balance between IL-17 producing dTh17 cells and FoxP3 dTreg cells was not altered. Acute GVHD induced with IL-21R KO splenocytes resulted in an attenuated disease phenotype as indicated by a significant decrease in dCD4 and CD8 engraftment, decreased host B cell elimination (90%±0.3) compared to wt injected mice (57%±6; p=0.03), decreased anti-host CTL activity and increased anti-ssDNA Ab levels. These results suggest that IL-21/IL-21R interaction on T cells promotes lupus-like cGVHD by sustaining TFH cell number yet it downregulates the humoral component in aGVHD by enhancing host B cells elimination by CTL.

Discontinuation of antiretroviral therapy causing progression to end-stage renal disease in an HIV patient diagnosed with immune complex 'lupus-like' glomerulonephritis.

Immune complex ‘lupus-like glomerulonephritis’ is a type of renal injury seen infrequently in human immunodeficiency virus (HIV) patients and very little is known about the clinical course and treatment. Treatment options are limited but antiretroviral therapy and steroids have been tried with limited success. We report a case of a 21-year-old HIV-positive African American male with lupus-like glomerulonephritis who progressed to end-stage renal disease upon discontinuation of highly active antiretroviral therapy. This case illustrates the importance of antiretroviral therapy as an important treatment modality for immune complex lupus-like glomerulonephritis in HIV patients.

Newly Diagnosed White Man With HIV-Associated Lupus-Like Nephropathy

AbstractAlthough HIV-associated nephropathy (HIVAN) is the most common form of glomerulopathy found in HIV-infected patients, other lesions have been reported. Lupus-like glomerulonephritis is a lesion that presents with diffuse proliferative immune-complex trapping with lupus-like features instead