title: Elevated urinary excretion of immunoglobulins in nonproteinuric patients with type 1 diabetes.
abstract: Increased albuminuria is a hallmark of early diabetic nephropathy, whereas the role of immunoglobulins (Igs), such as IgG (its 1-4 subtypes), IgA, and IgM, different in charge and size, has not been examined in early nephropathy in the past due to lack of a sensitive and reliable method. Our study group consisted of subjects with type 1 diabetes (T1D) and normoalbuminuria (n = 78), microalbuminuria (n = 78), and of 75 healthy subjects (HS). A Luminex-based immunoassay (1,000 time more sensitive than nephelometry-based method) was validated for the urine matrix and used for the measurements of IgG1-4, IgA, and IgM in our study groups. The Luminex-based assay detected Igs in 87% of HS subjects and in 100% of T1D subjects. Recovery of known amounts of Igs added to urine was 92-118%. In the normoalbuminuria group, urinary concentrations of albumin, IgG2, IgA, and IgM were significantly higher than in HS, whereas in the microalbuminuria, further elevation of IgG2, IgG4, and IgA was the most pronounced. In all three groups, fractional excretion of Igs was at least 100 times lower than that of albumin. Fractional excretion of IgG2 was the highest among all Igs. We validated a sensitive method for measuring Igs in urine using Luminex. We found that elevated concentrations of Igs, particularly in IgG2 and IgA, is present in subjects with T1D and no proteinuria. Elevation of those particular Ig subtypes suggests a contribution of novel mechanisms in early diabetic nephropathy, different from charge and size barrier impairment.
authors.affiliation: Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Gohda
authors.forename: William H
authors.initials: WH
authors.lastname: Walker
authors.forename: Pawel
authors.initials: P
authors.lastname: Wolkow
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: James H
authors.initials: JH
authors.lastname: Warram
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Krolewski
authors.forename: Monika A
authors.initials: MA
authors.lastname: Niewczas
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D003928:Diabetic Nephropathies / Q000652:urine*; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000652:urine*; D008297:Male; D011507:Proteinuria / Q000652:urine
chemical_list: D007136:Immunoglobulins