Immunofluorescence Staining for Immunoglobulin Heavy Chain/Light Chain on Kidney Biopsies is a Valuable Ancillary Technique For the Diagnosis of Monoclonal Gammopathy-Associated Kidney Diseases
blogged by Amélie Dendooven
Samih H. Nasr, Mary E. Fidler, Samar M. Said, Justin W. Koepplin, Jamie M. Altamirano-Alonso, Nelson Leung. Kidney International. Published online: March 24, 2021. DOI:https://doi.org/10.1016/j.kint.2021.02.038
This recent article in KI describes the use of a new set of antibodies targeted against heavy-light Ig chain pairs for immunofluorescence on frozen sections.
For many years, immune studies for IgG, IgM, IgA, C3c, kappa and lambda have been standard in the work-up of kidney biopsies, sometimes supplemented with stainings for fibrinogen, albumin and IgG1, IgG2, IgG3, IgG4 subtypes amongst others.
More recently, different types of monoclonal immunoglobulin-associated kidney diseases have emerged where linkage of disease morphology to a culprit clone is important for therapeutic purposes, especially since a circulating clone is not always present in blood or bone marrow. Thus, ancillary techniques that can supplement classical IF are welcomed.
In this paper, the authors describe antibodies against the epitope at the junction of CH1 and CL of intact heavy/light chain pairs IgGkappa, IgGlambda, IgAkappa, IgAlambda, IgMkappa, IgMlambda for direct IF, named HLC antibodies. According to the authors, HLC IF provides a solution for difficult IF patterns where monoclonality is in the differential diagnosis. E.g., from 10 cases of proliferative GN with monoclonal immune deposits (PGNMID), 2 proved to be polyclonal with HLC IF. Half of tested cases of DNAJB9-associated ’monotypic’ fibrillary GN proved to be polytypic with HLC IF. The assay was of value in subtyping cryoglobulinemic GN, especially for differentiation of true type II cryoglobulinemic GN from type III.
Some questions remain:
-How does the HLC IF technique perform compared to non antibody-antigen based assays?
-How does IF with HLC antibodies on frozen tissue compare to current unmasking techniques on FFPE and what is the optimal sequence to perform testing?
-Can the HLC antibodies also be used for indirect IF or immunohistochemistry on paraffin material?
-Are findings similar in different laboratories (external validation)?
-Some diseases are incompletely covered in this paper (eg monotypic membranous GN, immunotactoid GN). How does HLC IF perform there?
Nevertheless, the paper introduces another potentially valuable tool to the armamentarium of the nephropathologist.