[PDF][PDF] Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy

M Gödel, F Grahammer, TB Huber - N Engl J Med, 2015 - researchgate.net
N Engl J Med, 2015researchgate.net
To the Editor: The seminal discoveries identifying phospholipase A2 receptor (PLA2R) 1
and, most recently by Tomas et al.(Dec. 11 issue), 2 thrombospondin type-1 domain-
containing 7A (THSD7A) as commonly targeted podocyte autoantigens in idiopathic
membranous nephropathy herald a new era in the diagnosis of the disorder. Translating this
knowledge into a lucid pathomechanistic understanding of involved immune-complex
formation and subsequent molecular injury signaling, however, has been hampered by the …
To the Editor: The seminal discoveries identifying phospholipase A2 receptor (PLA2R) 1 and, most recently by Tomas et al.(Dec. 11 issue), 2 thrombospondin type-1 domain-containing 7A (THSD7A) as commonly targeted podocyte autoantigens in idiopathic membranous nephropathy herald a new era in the diagnosis of the disorder. Translating this knowledge into a lucid pathomechanistic understanding of involved immune-complex formation and subsequent molecular injury signaling, however, has been hampered by the absence of PLA2R in rodent podocytes. 3 Using RNA-sequencing analysis of freshly isolated, pure murine podocyte fractions, we found that, unlike PLA2R, THSD7A is highly and specifically enriched in podocytes (Fig. 1A). Furthermore, immunogold labeling identified THSD7A as a protein that specifically localizes to podocyte endocytic compartments, foot processes, and the slit diaphragm (Fig. 1B). These data regarding THSD7A indicate that there is a unique opportunity to rapidly transfer the discovery of Tomas et al. into experimental models, which should facilitate understanding of the molecular pathophysiological events that drive human idiopathic membranous ne phropathy.
researchgate.net