Peter D Burbelo1, Megha Joshi2, Adrija Chaturvedi1, Dustin J Little2, John S Thurlow2, Meryl Waldman3, Stephen W Olson4. 1. Dental Clinical Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland. 2. Nephrology Department, Walter Reed National Military Medical Center, Bethesda, Maryland; and. 3. Kidney Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. 4. Nephrology Department, Walter Reed National Military Medical Center, Bethesda, Maryland; and stephen.w.olson.mil@mail.mil.
Abstract
BACKGROUND: Circulating serum autoantibodies against the M-type phospholipase A2 receptor (PLA2R-AB) are a key biomarker in the diagnosis and monitoring of primary membranous nephropathy (MN). However, little is known about the appearance and trajectory of PLA2R-AB before the clinical diagnosis of MN. METHODS: Using the Department of Defense Serum Repository, we analyzed PLA2R-AB in multiple, 1054 longitudinal serum samples collected before diagnosis of MN from 134 individuals with primary MN, 35 individuals with secondary MN, and 134 healthy volunteers. We evaluated the presence and timing of non-nephrotic range proteinuria (NNRP) and serum albumin measurements in relation to PLA2R-AB status. RESULTS: Analysis of PLA2R-AB in longitudinal serum samples revealed seropositivity in 44% (59 out of 134) of primary MN cases, 3% (one out of 35) of secondary MN cases, and in 0% of healthy controls. Among patients with MN, PLA2R-AB were detectable at a median of 274 days before renal biopsy diagnosis (interquartile range, 71-821 days). Approximately one third of the participants became seropositive within 3 months of MN diagnosis. Of the 21 individuals with documented prediagnostic NNRP, 43% (nine out of 21) were seropositive before NNRP was first documented and 28.5% (six out of 21) were seropositive at the same time as NNRP; 66% (39 out of 59) of those seropositive for PLA2R-AB had hypoalbuminemia present at the time antibody was initially detected. Twelve participants (20%) were seropositive before hypoalbuminemia became apparent, and eight participants (14%) were seropositive after hypoalbuminemia became apparent. CONCLUSIONS: Circulating PLA2R-AB are detectable months to years before documented NNRP and biopsy-proven diagnosis in patients with MN.
BACKGROUND: Circulating serum autoantibodies against the M-type phospholipase A2 receptor (PLA2R-AB) are a key biomarker in the diagnosis and monitoring of primary membranous nephropathy (MN). However, little is known about the appearance and trajectory of PLA2R-AB before the clinical diagnosis of MN. METHODS: Using the Department of Defense Serum Repository, we analyzed PLA2R-AB in multiple, 1054 longitudinal serum samples collected before diagnosis of MN from 134 individuals with primary MN, 35 individuals with secondary MN, and 134 healthy volunteers. We evaluated the presence and timing of non-nephrotic range proteinuria (NNRP) and serum albumin measurements in relation to PLA2R-AB status. RESULTS: Analysis of PLA2R-AB in longitudinal serum samples revealed seropositivity in 44% (59 out of 134) of primary MN cases, 3% (one out of 35) of secondary MN cases, and in 0% of healthy controls. Among patients with MN, PLA2R-AB were detectable at a median of 274 days before renal biopsy diagnosis (interquartile range, 71-821 days). Approximately one third of the participants became seropositive within 3 months of MN diagnosis. Of the 21 individuals with documented prediagnostic NNRP, 43% (nine out of 21) were seropositive before NNRP was first documented and 28.5% (six out of 21) were seropositive at the same time as NNRP; 66% (39 out of 59) of those seropositive for PLA2R-AB had hypoalbuminemia present at the time antibody was initially detected. Twelve participants (20%) were seropositive before hypoalbuminemia became apparent, and eight participants (14%) were seropositive after hypoalbuminemia became apparent. CONCLUSIONS: Circulating PLA2R-AB are detectable months to years before documented NNRP and biopsy-proven diagnosis in patients with MN.
Authors: Stephen W Olson; Charles B Arbogast; Thomas P Baker; David Owshalimpur; David K Oliver; Kevin C Abbott; Christina M Yuan Journal: J Am Soc Nephrol Date: 2011-08-25 Impact factor: 10.121
Authors: Peter D Burbelo; Sarah M Gordon; Meryl Waldman; Jess D Edison; Dustin J Little; Rodger S Stitt; Wayne T Bailey; James B Hughes; Stephen W Olson Journal: PLoS One Date: 2019-03-26 Impact factor: 3.240
Authors: Maryline Fresquet; Thomas A Jowitt; Jennet Gummadova; Richard Collins; Ronan O'Cualain; Edward A McKenzie; Rachel Lennon; Paul E Brenchley Journal: J Am Soc Nephrol Date: 2014-10-06 Impact factor: 10.121
Authors: Elion Hoxha; Rolf A K Stahl; Linda Reinhard; Alexander Kühnl; Wolfgang Schlumberger; Cornelia Dähnrich Journal: Kidney Int Rep Date: 2021-01-13