Gene/Protein Disease Symptom Drug Enzyme Compound
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We report a case of squamous cell lung cancer with nephrotic syndrome. A 69-year-old man was admitted because of proteinuria and microhematuria. A plain chest X-ray film on admission showed a large mass in the left-lower lung field. The patient was given a diagnosis of minimal-change-nephrotic syndrome and squamous cell lung cancer. We first treated the nephrotic syndrome with glucocorticoid therapy, and then treated the lung cancer with chemo-radiotherapy. This reduced the lung cancer, alleviated the proteinuria, and completely resolved the nephrotic syndrome. Nephrotic syndrome is generally associated with malignant lymphoma and other nonepithelial neoplasms. As the underlying disease, epithelial neoplasms are less common, but lung cancer is one of the most widely reported. Histologically, most cases of cancer-associated nephrotic syndrome exhibit membranous nephropathy; Minimal-change nephrotic syndrome is rare. Deposits of immunocomplex on glomerular basement membrane are considered to play a pathogenic role in membranous nephropathy. However, the pathogenesis of minimal-change nephrotic syndrome is different.
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PMID:[Squamous cell lung cancer with minimal-change nephrotic syndrome]. 1006 57

Serum autoantibodies to the glycolytic enzyme enolase have been reported in a diverse range of inflammatory, degenerative, and psychiatric disorders. Diseases in which these antibodies have been reported in high incidence include autoimmune polyglandular syndrome type 1 (80%, 35 of 44), primary (69%, 60 of 87), and secondary (58%, 14 of 24) membranous nephropathy, cancer-associated retinopathy (68.8%, 11 of 16), autoimmune hepatitis type 1 (60%, 12 of 20), mixed cryoglobulinemia with renal involvement (63.6%, seven of 11), cystoid macular edema (60%, six of 10), and endometriosis (50%, 21 of 41). In autoimmune polyglandular syndrome type 1 patients, all had chronic mucocutaneous candidiasis with demonstrated antibody reactivity to candida enolase, which is suggestive of cross reactivity or epitope mimicry. Formation of autoantibodies to enolase may be a normal process, with reported incidence in apparently healthy subjects ranging from 0% (zero of 91) to 11.7% (seven of 60). Nonetheless, we suggest that excessive production of these autoantibodies, which are generated as a consequence of uptake of enolase by antigen-presenting cells and subsequent B cell activation, can potentially initiate tissue injury as a result of immune complex deposition.
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PMID:Disease association, origin, and clinical relevance of autoantibodies to the glycolytic enzyme enolase. 1128 54

The association between membranous nephropathy (MN) and cancer is often mentioned in textbooks but poorly substantiated, and the characteristics of cancer-associated MN are unknown. To address these questions, we studied a cohort of 240 patients with MN, among them 24 had malignancy at the time of renal biopsy or within a year thereafter. The incidence of cancer was significantly higher in these patients than in the general population (standardized incidence ratio 9.8 [5.5-16.2] for men and 12.3 [4.5-26.9] for women). The frequency of malignancy increased with age. At the time of diagnosis, clinical presentation did not differ between the patients with cancer-associated MN and those with idiopathic MN, but smoking was more frequent among patients with cancer. Analysis of renal biopsies revealed that the number of inflammatory cells infiltrating the glomeruli was significantly higher in patients with cancer-associated MN (P = 0.001). The best cutoff value for distinguishing malignancy-related cases from controls was eight cells per glomerulus. Using this threshold led to a diagnosis of cancer-associated MN with a specificity of 75% and a sensitivity of 92%. In patients with cancer-associated MN, there was a strong relationship between reduction of proteinuria and clinical remission of cancer (P < 0.001). In conclusion, our study provides epidemiologic evidence of an excess of cancer risk in patients with MN. It also shows that age, smoking, and the presence of glomerular leukocytic infiltrates strongly increase the likelihood of malignancy in MN patients.
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PMID:Membranous nephropathy and cancer: Epidemiologic evidence and determinants of high-risk cancer association. 1694 Oct 21

Many solid and hematological malignancies have been associated with different glomerular diseases. Several case reports and case series of cancer-associated glomerular diseases have shown that treating the cancer may lead to resolution of the glomerular process. Hence, knowledge and approach to cancer-associated glomerular diseases is important for both the caring nephrologists and the cancer specialists. While membranous nephropathy has been classically associated with solid malignancies, minimal change disease has been commonly described with hematologic malignancies, especially non-Hodgkin's lymphoma. Membranoproliferative glomerulonephritis is increasingly being recognized to be associated with chronic hematologic malignancies such as chronic lymphocytic leukemia. In this article, we review various cancer-associated glomerular diseases and their pathogenesis as well as principles of treatment. In addition, we also review glomerular diseases seen after chemotherapy and hematopoietic stem cell transplantation.
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PMID:Glomerular diseases associated with cancer, chemotherapy, and hematopoietic stem cell transplantation. 2435 86

Membranous nephropathy (MN) is an autoimmune disease caused by binding of circulating antibodies to podocyte antigens in the kidney. For decades and still today primary MN has been considered to have an unspecified IgG4-driven autoimmune genesis, while secondary MN has been associated with other diseases, most notably cancer, and not linked to IgG4. Immunologic mechanisms of primary and malignancy-associated MN are assumed to be different, however, this has never been systematically evaluated. The identification of Phospholipase A2 Receptor 1 (PLA2R1) and Thrombospondin Type-1 Domain-Containing 7A (THSD7A) as target antigens in MN allows a pathogenesis-driven differential diagnosis. Recent data showing a molecular link between increased THSD7A-expression in tumors and THSD7A-antibody positive MN suggest a similar pathogenesis of malignancy-associated and primary MN. In order to better define the underlying immunologic processes, we systematically analyzed circulating antigen-specific IgG subclasses in the serum of 76 patients with PLA2R1-associated MN and 41 patients with THSD7A-associated MN in relationship to concurrent malignancy and disease outcome. Twenty-three patients in the study had malignancy-associated MN. We analyzed antigen-specific IgG subclasses in the serum of all patients at baseline and in 55 patients during follow-up by Western blot applying antigens derived from human kidney and lung. At baseline all 117 patients were positive for IgG4-antibodies against either PLA2R1 or THSD7A, while IgG3, IgG1, and IgG2-antibodies were found in 87, 72, and 26% of patients, respectively. There were no differences in the IgG subclass distribution between patients with primary vs. cancer-associated MN and no association with disease outcome. Moreover, levels of antigen-specific IgG4-antibodies were not different between primary and malignancy-associated MN and levels of all IgG subclasses did not differ between these groups. Both podocytes and lung bronchioles showed expression of both PLA2R1 and THSD7A when analyzed by immunofluorescence and Western blot. Every antigen-specific IgG subclass showed identical binding in both organs and autoantibodies bound the respective antigen only under non-reducing conditions. We conclude that antigen-specific IgG subclasses do not differentiate primary from malignancy-associated MN or predict disease prognosis. These data support the view that one common pathway may lead to primary and cancer-associated MN induced by PLA2R1- or THSD7A-antibodies.
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PMID:Antigen-Specific IgG Subclasses in Primary and Malignancy-Associated Membranous Nephropathy. 3061 70