IgG4-related kidney disease: experience from a Mexican cohort.

To evaluate the clinical/serological phenotype and outcomes of IgG4-related kidney disease. Case series of IgG4-related kidney disease from a cohort of 69 patients with IgG4-related disease. We defined kidney involvement as the presence of at least one of the following conditions: (A) laboratory parameters of kidney injury (proteinuria and/or elevated creatinine levels and/or hematuria); and/or (B) contrast-enhanced computed tomography features (multiple low-density lesions and/or nephromegaly and/or hypovascular solitary mass and/or renal pelvic lesion and/or perinephric lesions). We identified 17 patients with kidney involvement (24.6%), with a mean age of 53.6 ± 11.3 years; thirteen (76.5%) were male. Six patients fulfilled the laboratory criteria, six the imaging criteria, and five both. Five patients had a renal biopsy, the main histopathological diagnosis being IgG4 tubulointerstitial nephritis. Sixteen patients received glucocorticoids and 12 also immunosuppressors and/or biologics. Sixteen patients presented either total or partial renal remission at a median follow-up of 26 months, while one patient developed end-stage renal disease. Patients with kidney disease, as opposed to patients without kidney involvement, had a higher number of involved organs, higher IgG4-related disease responder index and IgG4 and IgG1 serum levels, higher prevalence of rheumatoid factor, and lower C3 and C4 levels. Our study emphasizes the systemic nature of IgG4-related disease, highlighting that renal involvement is usually present in a subset of patients with multisystemic disease, high IgG1 and IgG4 levels, and hypocomplementemia. Key Points • IgG4-RKD presents at a younger age in Mexican mestizo patients. • IgG4-RKD presents with proteinuria and kidney injury or as an asymptomatic imaging finding. • IgG4-RKD presents in the context of multisystemic disease, hypocomplementemia, and high IgG1 and IgG4 levels.

Systemic BK Virus Infection in a Pediatric Patient With Severe Combined Immunodeficiency.

Human BK virus (BKV) infection is known to occur mostly during childhood with the establishment of latent infection with no tissue damage or clinical manifestations. However, conditions causing immunosuppression can lead to increased virus replication and tissue damage. Although the tissues most commonly involved are the kidneys, bladder, ureters and, to some extent, brain tissue, there are some reports that suggest that BKV may cause multisystemic infections. In this case, a 12-month-old child was seen to suffer from multiple gastrointestinal infections. This prompted a search for immunodeficiencies, which revealed the presence of severe combined immunodeficiency. The child was eventually hospitalized and continued showing recurrent bouts of gastroenteritis as well as lower respiratory infection. After multiple antibiotic courses, he developed acute kidney injury, a hemophagocytic syndrome, and eventually respiratory failure, which led to his death a year later. Autopsy findings revealed the presence of a disseminated BKV infection involving the kidneys, ureters, leptomeninges, and pancreas. Analysis of the literature failed to show any previous case of BKV pancreatitis. The present case suggests that BKV can damage more tissues than previously reported and may be responsible for systemic infections in immunosuppressed patients.

A Unique Cellular and Molecular Microenvironment Is Present in Tertiary Lymphoid Organs of Patients with Spontaneous Prostate Cancer Regression.

OBJECTIVE: Multiple solid cancers contain tertiary lymphoid organs (TLO). However, it is unclear whether they promote tumor rejection, facilitate tumor evasion, or simply whether they are a byproduct of chronic inflammation. We hypothesize that although chronic inflammation induces TLO formation, the tumor milieu can modulate TLO organization and functions in prostate cancer. Therefore, our study seeks to elucidate the cellular and molecular signatures in unique prostatectomy specimens from evanescent carcinoma patients to identify markers of cancer regression, which could be harnessed to modulate local immunosuppression or potentially enhance TLO function. METHODS: We used multicolor immunofluorescence to stain prostate tissues, collected at different stages of cancer progression (prostatic intraepithelial neoplasia, intermediate and advanced cancer) or from patients with evanescent prostate carcinoma. Tissues were stained with antibodies specific for pro-inflammatory molecules (cyclooxygenase 2, CXCL10, IL17), tumor-infiltrating immune cells (mature DC-LAMP+ dendritic cells, CD3+ T cells, CD3+Foxp3+ regulatory T cells (Treg), T bet+ Th1 cells, granzyme B+ cytotoxic cells), and stromal cell populations (lymphatic vessels, tumor neovessels, high endothelial venules (HEV), stromal cells), which promote prostate tumor growth or are critical components of tumor-associated TLO. RESULTS: Generally, inflammatory cells are located at the margins of tumors. Unexpectedly, we found TLO within prostate tumors from patients at different stages of cancer and in unique samples from patients with spontaneous cancer remission. In evanescent prostate carcinomas, accumulation of Treg was compromised, while Tbet+ T cells and CD8 T cells were abundant in tumor-associated TLO. In addition, we found a global decrease in tumor neovascularization and the coverage by cells positive for cyclooxygenase 2 (COX2). Finally, consistent with tumor regression, prostate stem cell antigen was considerably reduced in TLO and tumor areas from evanescent carcinoma patients. CONCLUSION: Collectively, our results suggest that COX2 and Treg are attractive therapeutic targets that can be harnessed to enhance TLO-driven tumor immunity against prostate cancer. Specially, the presence of HEV and lymphatics indicate that TLO can be used as a platform for delivery of cell-based and/or COX2 blocking therapies to improve control of tumor growth in prostate cancer.