Anti-neutrophil cytoplasmic antibody-associated vasculitides (AAV) are rare autoimmune disorders typically involving the lungs and kidneys. A few case reports have described an association with hematopoietic stem cell transplant (HSCT). We present a case of myeloperoxidase-positive AAV with predominant renal involvement in a 49-year-old male with a history of acute myeloid leukemia treated with allogenic HSCT and complicated by chronic graft-versus-host disease (GVHD). He presented with rapidly progressive glomerulonephritis, and kidney biopsy revealed pauci-immune necrotizing crescentic glomerulonephritis. Treatment with methylprednisolone pulses followed by oral prednisolone, rituximab, and plasmapheresis led to improved kidney function and a tailored rituximab maintenance regimen was followed. However, a renal-limited relapse occurred at 15 months, requiring repeat induction therapy. Dialysis was avoided, but renal function only partially recovered. This case suggests that AAV can develop after HSCT and GVHD and highlights the importance of long-term follow-up and further research into underlying mechanisms.

BACKGROUND/OBJECTIVES: Indole-3-propionic acid (IPA) is a tryptophan-derived microbial metabolite that has been associated with protective effects against inflammatory and metabolic diseases. However, there is a lack of knowledge regarding the effects of IPA under physiological conditions and at the intestinal level.MATERIALS/METHODS: Human intestinal epithelial Caco-2 cells were treated for 2, 24, and/ or 72 h with IPA or its precursors – indole, tryptophan, and propionate – at 1, 10, 100, 250, or 500 μM to assess cell viability, integrity, differentiation, and proliferation. RESULTS: IPA induced cell proliferation and this effect was associated with a higher expression of extracellular signal-regulated kinase 2 (ERK2) and a lower expression of c-Jun. Although indole and propionate also induced cell proliferation, this involved ERK2 and c-Jun independent mechanisms. On the other hand, both tryptophan and propionate increased cell integrity and reduced the expression of claudin-1, whereas propionate decreased cell differentiation. CONCLUSIONS In conclusion, these findings suggested that IPA and its precursors distinctly contribute to the proliferation, differentiation, and barrier function properties of human intestinal epithelial cells. Moreover, the pro-proliferative effect of IPA in intestinal epithelial cells was not explained by its precursors and is rather related to its whole chemical structure.Maintaining IPA at physiological levels, e.g., through IPA-producing commensal bacteria, may be important to preserve the integrity of the intestinal barrier and play an integral role in maintaining metabolic homeostasis.

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