Monthly plasmapheresis for systemic lupus erythematosus with diffuse proliferative glomerulonephritis: a pilot study

Twelve patients with systemic lupus erythematosus and biopsy-proved diffuse proliferative glomerulonephritis were randomly allocated to a control group (to continue receiving conventional therapy only) or to a plasmapheresis group (to receive conventional therapy along with one 4-I plasma exchange a month). The six patients treated with plasmapheresis had better preservation of renal function, reduced disease activity, fewer admissions to hospital and less need for steroid and immunosuppressive therapy than the six control patients. The patients treated with plasmapheresis also showed evidence of reduced immunologic activity and had no side effects attributable to the plasma exchange. These results suggest that monthly plasma exchange should be assessed in a controlled randomized trial as a possible therapeutic adjunct in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis.     

Identification of urinary metabolites that distinguish membranous lupus nephritis from proliferative lupus nephritis and focal segmental glomerulosclerosis

Introduction

Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease, and kidney involvement with SLE, a.k.a. lupus nephritis (LN), is a frequent and severe complication of SLE that increases patient morbidity and mortality. About 50% of patients with SLE encounter renal abnormalities which, if left untreated, can lead to end-stage renal disease. Kidney biopsy is considered the criterion standard for diagnosis and staging of LN using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, which was developed to help predict renal outcomes and assist with medical decision-making. However, kidney biopsy-based classification of LN is highly invasive and impractical for real-time monitoring of LN status. Here, nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling was used to identify urinary metabolites that discriminated between proliferative and pure membranous LN as defined by the ISN/RPS classification, and between LN and primary focal segmental glomerulosclerosis (FSGS).

Methods

Metabolic profiling was conducted using urine samples of patients with proliferative LN without membranous features (Class III/IV; n = 7) or pure membranous LN (Class V; n = 7). Patients with primary FSGS and proteinuria (n = 10) served as disease controls. For each patient, demographic information and clinical data was obtained and a random urine sample collected to measure NMR spectra. Data and sample collection for patients with LN occurred around the time of kidney biopsy. Metabolic profiling analysis was done by visual inspection and principal component analysis.

Results

Urinary citrate levels were 8-fold lower in Class V LN compared to Class III/IV patients, who had normal levels of urinary citrate (P < 0.05). Class III/IV LN patients had > 10-fold lower levels of urinary taurine compared to Class V patients, who had mostly normal levels (P < 0.01). Class V LN patients had normal urinary hippurate levels compared to FSGS patients, who completely lacked urinary hippurate (P < 0.001).

Conclusions

This pilot study indicated differences in urinary metabolites between proliferative LN and pure membranous LN patients, and between LN and FSGS patients. If confirmed in larger studies, these urine metabolites may serve as biomarkers to help discriminate between different classes of LN, and between LN and FSGS.     

Mycophenolate mofetil as maintenance therapy for proliferative lupus nephritis: a long-term observational prospective study

Introduction  

While the role of mycophenolate mofetil (MMF) in the management of lupus nephritis has been increasingly recognized, limited information is available regarding its efficacy and safety as a long-term maintenance treatment. The aim of the present study was to evaluate the efficacy and safety profile of MMF as maintenance therapy for proliferative lupus nephritis.     

Extragonadal germ cell tumor presenting in a woman with systemic lupus erythematosus: a case report

Introduction

Esophageal intramural pseudodiverticulosis is a rare condition characterized by the dilatation of the submucosal glands.

Case presentation

We present a case of esophageal intramural pseudodiverticulosis in a 72-year-old Caucasian man who presented with dysphagia and with a background history of alcohol abuse. An upper gastrointestinal endoscopy of our patient showed an esophageal stricture with abnormal mucosal appearances, but no malignant cells were seen at biopsy. Appearances on a barium esophagram were pathognomonic for esophageal intramural pseudodiverticulosis.

Conclusion

We demonstrate the enduring usefulness of barium esophagography in the characterization of abnormal mucosal appearances at endoscopy.     

Histological antiphospholipid-associated nephropathy versus lupus nephritis in patients with systemic lupus erythematosus: an observational cross-sectional study with longitudinal follow-up

IntroductionRenal involvement is a severe complication in systemic lupus erythematosus (SLE). Moreover, a subset of SLE patients develop the anti-phospholipid syndrome (APS), characterised by the occurrence of anti-phospholipid antibodies in combination with macro- and microvascular thrombotic manifestations, including acute and chronic antiphospholipid-associated nephropathy (APLN). Clinical presentations of lupus nephritis and APLN are similar and a renal biopsy is necessary to differentiate between the conditions. Our aim with this study was to investigate the occurrence of histopathological findings consistent with APLN (hAPLN) in renal biopsies from SLE patients and to investigate associations with anti-phospholipid antibody specificities, clinical manifestations, HLA-DRB1 alleles, and long-term renal outcome.MethodConsecutive renal biopsies from 112 SLE patients with renal involvement were investigated and evaluated for findings of hAPLN; in all there were 236 renal biopsies. Data from biopsy reports and clinical information were collected. Autoantibodies against cardiolipin and β₂-glycoprotein-1 were measured by enzyme-linked immunosorbent assay. A lupus anticoagulant test was determined with a modified Dilute Russel Viper Venom method. HLA genotyping was performed by sequence-specific primer PCR. Renal outcome was determined at study end.ResultsThe prevalence of hAPLN was 14.3% among SLE patients with renal involvement. Compared to patients with pure lupus nephritis, occurrence of hAPLN was associated with intima changes (odds ratio (OR) = 24; 95% confidence interval (CI), 3.0 to 189.8; P < 0.0001), hypertensive vascular changes (OR = 7.8; 95% CI, 1.6 to 39.4; P = 0.01), inflammatory infiltrates (OR = 6.5; 95% CI, 1.7 to 25.1; P = 0.007) and tubular atrophy (OR = 13.1; 95% CI, 1.7 to 103.6; P = 0.002). hAPLN was associated with the presence of cardiolipin antibodies (OR = 3.3; 95% CI, 1.0 to 10.8; P = 0.05) and triple anti-phospholipid antibody positivity (OR = 4.2; 95% CI, 1.3 to 13.7; P = 0.02). Patients with hAPLN were more hypertensive (OR = 3.8; 95% CI, 1.2 to 12.3; P = 0.03) and had higher levels of creatinine as compared to lupus nephritis patients (median 116 versus 75 μmol/L; P < 0.0001). We found significantly higher frequency of HLA-DRB1*13 (OR = 5.1; 95% CI, 1.7 to 15.4; P = 0.03) and development of end-stage renal disease (OR = 5.8; 95% CI, 1.7 to 19.7; P = 0.008) in hAPLN compared with lupus nephritis.ConclusionhAPLN is a severe and often unrecognized condition in SLE patients with renal involvement. We have demonstrated an increased risk for development of renal impairment and a genetic predisposition in hAPLN patients compared to lupus nephritis patients.     

Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis

Introduction

Microthrombosis is often observed in lupus nephritis (LN) lesions, but its clinical significance is unknown. We evaluated the clinicopathologic correlations of renal microthrombosis and inflammatory markers in LN.

Methods

Kidney biopsies from 58 patients with systemic lupus erythematosus (SLE) proliferative nephritis were analyzed with immunohistochemistry (IHC) for intravascular platelet aggregates (CD61), macrophagic infiltration (CD68), and activated complement deposition (C4d). Clinical data at the time of kidney biopsy and follow-up were analyzed with regard to pathologic IHC data.

Results

Microthrombosis was present in 52% of the tissues. It was significantly more prevalent in patients with antiphospholipid antibodies (aPLs) (62% versus 42%). The presence of microthrombosis significantly correlated with higher macrophagic infiltration. Macrophagic infiltration but not microthrombosis was significantly correlated with C4d deposition. Only macrophagic infiltration showed a correlation with SLE and renal activity (proteinuria and active sediment), whereas neither the presence of CD61⁺ microthrombi nor the extent of C4d deposition correlated with LN severity or outcome.

Conclusions

Microthrombosis is associated with higher macrophagic infiltration in LN but does not seem to increase independently the severity of renal damage. Macrophagic infiltration was the best marker of SLE and renal activity in this LN series.     

Treatment with a laminin-derived peptide suppresses lupus nephritis

The role of DNA as the target for pathogenic lupus autoantibodies in systemic lupus erythematosus is equivocal and renal damage may be due to cross-reactivity of lupus Abs with glomerular components. We have previously shown that lupus autoantibodies bind to the laminin component of the extracellular matrix. In the present work, we have analyzed the fine specificity of the interaction of pathogenic murine lupus autoantibodies with this molecule and the effect of inhibiting their binding to laminin during the course of the disease. We have found that pathogenic murine lupus autoantibodies react with a 21-mer peptide located in the globular part of the alpha-chain of laminin. Immunization of young lupus-prone mice with this peptide accelerated renal disease. Analysis of transgenic, congenic, and RAG-1(-/-) mice confirmed the importance of this epitope in the pathogenesis of lupus renal disease. We have synthesized a panel of peptides that cross-react with the anti-laminin Abs and have found that the binding of lupus autoantibodies to the extracellular matrix could be inhibited in vitro by some of these competitive peptides. Treatment of MRL/lpr/lpr mice with these peptides prevented Ab deposition in the kidneys, ameliorated renal disease, and prolonged survival of the peptide-treated mice. We suggest that laminin components can serve as the target for lupus Abs. The interaction with these Ags can explain both the tissue distribution and the immunopathological findings in lupus. Moreover, inhibition of autoantibody binding to the extracellular matrix can lead to suppression of disease.     

Autoantigen microarrays reveal autoantibodies associated with proliferative nephritis and active disease in pediatric systemic lupus erythematosus

IntroductionPediatric systemic lupus erythematosus (pSLE) patients often initially present with more active and severe disease than adults, including a higher frequency of lupus nephritis. Specific autoantibodies, including anti-C1q, anti-DNA and anti-alpha-actinin, have been associated with kidney involvement in SLE, and DNA antibodies are capable of initiating early-stage lupus nephritis in severe combined immunodeficiency (SCID) mice. Over 100 different autoantibodies have been described in SLE patients, highlighting the need for comprehensive autoantibody profiling. Knowledge of the antibodies associated with pSLE and proliferative nephritis will increase the understanding of SLE pathogenesis, and may aid in monitoring patients for renal flare.MethodsWe used autoantigen microarrays composed of 140 recombinant or purified antigens to compare the serum autoantibody profiles of new-onset pSLE patients (n = 45) to healthy controls (n = 17). We also compared pSLE patients with biopsy-confirmed class III or IV proliferative nephritis (n = 23) and without significant renal involvement (n = 18). We performed ELISA with selected autoantigens to validate the microarray findings. We created a multiple logistic regression model, based on the ELISA and clinical information, to predict whether a patient had proliferative nephritis, and used a validation cohort (n = 23) and longitudinal samples (88 patient visits) to test its accuracy.ResultsFifty autoantibodies were at significantly higher levels in the sera of pSLE patients compared to healthy controls, including anti-B cell-activating factor (BAFF). High levels of anti-BAFF were associated with active disease. Thirteen serum autoantibodies were present at significantly higher levels in pSLE patients with proliferative nephritis than those without, and we confirmed five autoantigens (dsDNA, C1q, collagens IV and X and aggrecan) by ELISA. Our model, based on ELISA measurements and clinical variables, correctly identified patients with proliferative nephritis with 91 % accuracy.ConclusionsAutoantigen microarrays are an ideal platform for identifying autoantibodies associated with both pSLE and specific clinical manifestations of pSLE. Using multiple regression analysis to integrate autoantibody and clinical data permits accurate prediction of clinical manifestations with complex etiologies in pSLE.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0682-6) contains supplementary material, which is available to authorized users.     

TWEAK: a novel biomarker for lupus nephritis?

Renal involvement is common in systemic lupus erythematosus. Early diagnosis of lupus nephritis (LN), allowing the instigation of appropriate therapy, remains an important clinical challenge. Current biomarkers in clinical practice are less than ideal, lacking both sensitivity and specificity. In the previous issue of Arthritis Research & Therapy, Schwartz and colleagues demonstrated the potential value of urinary TNF-like weak inducer of apoptosis (uTWEAK) as a biomarker for LN. They showed that uTWEAK is elevated in subjects with LN at diagnosis compared with those with systemic lupus erythematosus but no renal disease, and correlates with the degree of clinical disease activity. These data are thought-provoking and provide the platform for future longer-term studies.     

Primary pleural synovial sarcoma with diffuse pleural involvement: A case report

Synovial sarcoma (SS) is a mesenchymal tumor which generally affects the soft tissues of the extremities. Primary pleural synovial sarcoma (PPSS) is a very rare and aggressive subtype of SS. A 73-year-old male patient presented with chest-back pain and dyspnea. Hypermetabolic diffuse pleural lesions were detected in ¹⁸F-FDG PET/CT performed after pleural nodular thickenings were observed on CT. As the result of the molecular analysis performed in the excisional biopsy, SYT-SSX mutation was detected and the patient was diagnosed as SS. Pazopanib treatment was commenced. We are reporting a very rare case of PPSS with diffuse pleural involvement.     

Metastatic balloon cell melanoma: a case report

BACKGROUND: The protean morphology of malignant melanoma is diagnostically challenging. Balloon cell melanoma is a histologic variant composed predominantly or entirely of large cells with abundant, vacuolated cytoplasm. It shares the cytologic features of the other subcategories of malignant melanoma, such as discohesion, nuclear pleomorphism and intranuclear cytoplasmic pseudoinclusions, but generally lacks melanin pigment and, as the name would suggest, is characterized by the presence of numerous cytoplasmic vacuoles. CASE: A 55-year-old man presented with an enlarged right cervical lymph node. Clinically and radiographically this mass was considered to be metastatic; however, the patient had no known primary neoplasm. Fine needle aspiration biopsy (FNAB) and cytologic examination showed numerous discohesive, variably sized, malignant cells with abundant, vacuolated cytoplasm and pleomorphic nuclei with irregular nuclear contours, macronucleoli and frequent intranuclear cytoplasmic pseudoinclusions. Pigment was not identified. These features, along with strong immunohistochemical positivity for S-100, HMB-45 and Melan-A, suggested the diagnosis of balloon cell melanoma. A right parotidectomy and lymph node dissection were performed, and histologic tissue evaluation confirmed the diagnosis. CONCLUSION: This case of lymph node balloon cell melanoma metastasis was diagnosed by FNAB.