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- Al-Rabadi, Laith Farah, et al.
(författare)
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Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy
- 2021
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Ingår i: Journal of the American Society of Nephrology. - : American Society of Nephrology (ASN). - 1046-6673 .- 1533-3450. ; 32:7, s. 1666-1681
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Tidskriftsartikel (refereegranskat)abstract
- Background Identification of target antigens PLA2R, THSD7A, NELL1, or Semaphorin-3B can explain the majority of cases of primary membranous nephropathy (MN). However, target antigens remain unidentified in 15%-20% of patients. Methods A multipronged approach, using traditional and modern technologies, converged on a novel target antigen, and capitalized on the temporal variation in autoantibody titer for biomarker discovery. Immunoblotting of human glomerular proteins followed by differential immunoprecipitation and mass spectrometric analysis was complemented by laser-capture microdissection followed by mass spectrometry, elution of immune complexes from renal biopsy specimen tissue, and autoimmune profiling on a protein fragment microarray. Results These approaches identified serine protease HTRA1 as a novel podocyte antigen in a subset of patients with primary MN. Sera from two patients reacted by immunoblotting with a 51-kD protein within glomerular extract and with recombinant human HTRA1, under reducing and nonreducing conditions. Longitudinal serum samples from these patients seemed to correlate with clinical disease activity. As in PLA2R- and THSD7A- associated MN, anti-HTRA1 antibodies were predominantly IgG4, suggesting a primary etiology. Analysis of sera collected during active disease versus remission on protein fragment microarrays detected significantly higher titers of anti-HTRA1 antibody in active disease. HTRA1 was specifically detected within immune deposits of HTRA1-associated MN in 14 patients identified among three cohorts. Screening of 118 "quadruple-negative" (PLA2R-, THSD7A-, NELL1-, EXT2-negative) patients in a large repository of MN biopsy specimens revealed a prevalence of 4.2%. Conclusions Conventional and more modern techniques converged to identify serine protease HTRA1 as a target antigen in MN.
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| 2. |
- Zhao, Yang, et al.
(författare)
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Medical costs and out-of-pocket expenditures associated with multimorbidity in China: Quantile regression analysis
- 2021
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Ingår i: BMJ Global Health. - 2059-7908. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Objective Multimorbidity is a growing challenge in low-income and middle-income countries. This study investigates the effects of multimorbidity on annual medical costs and the out-of-pocket expenditures (OOPEs) along the cost distribution. Methods Data from the nationally representative China Health and Retirement Longitudinal Study (CHARLS 2015), including 10 592 participants aged ≥45 years and 15 physical and mental chronic diseases, were used for this nationally representative cross-sectional study. Quantile multivariable regressions were employed to understand variations in the association of chronic disease multimorbidity with medical cost and OOPE. Results Overall, 69.5% of middle-Aged and elderly Chinese had multimorbidity in 2015. Increased number of chronic diseases was significantly associated with greater health expenditures across every cost quantile groups. The effect of chronic diseases on total medical cost was found to be larger among the upper tail than those in the lower tail of the cost distributions (coefficients 12, 95% CI 6 to 17 for 10th percentile; coefficients 296, 95% CI 71 to 522 for 90th percentile). Annual OOPE also increased with chronic diseases from the 10th percentile to the 90th percentile. Multimorbidity had larger effects on OOPE and was more pronounced at the upper tail of the health expenditure distribution (regression coefficients of 8 and 84 at the 10th percentile and 75th percentile, respectively). Conclusion Multimorbidity is associated with escalating healthcare costs in China. Further research is required to understand the impact of multimorbidity across different population groups.
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