In Reply to 'IgG4-restricted anti-glomerular basement membrane autoantibodies targeting quaternary epitopes of native α345(IV) collagen'

摘要

We have read Dr Borza's comments1 on our report2 with interest. The patients we described in our article exhibited several features that distinguish them from other patients with anti-GBM disease, including demographics, clinical presentation, autoanti-body specificity, autoantibody subclass distribution, and clinical outcome.2 We do not know which of these features co-occurred by chance and which were ate linked by a pathogenetic mechanism to form a syndrome within the syndrome. Dr Borza's letter focuses on autoantibody specificity and IgG subclass distribution, as 2 of our mainly IgG4 anti-GBM sera reacted better with non-denatured antigen, which presumably is a consequence of reactivity with an epitope requiring the intact alpha345NC1 hexamers of type IV collagen. We apologize that we failed to recognize Dr Borza's article describing a serum with such specificity and IgG4 predominance." However, we think it is too early to draw conclusions regarding the clinical significance of such antibodies or their IgG subclass distribution in general, even though Dr Borza provides interesting data from his animal model. It is an intriguing possibility that anti-hexamer autoantibodies might be less toxic to renal capillaries, and are perhaps more toxic to the lung capillaries, but such a hypothesis needs to be addressed in larger studies.