GLOMERULITIS DURING ACUTE CELLULAR REJECTION MAY BE A SURROGATE MARKER OF VASCULITIS IN RENAL ALLOGRAFTS (BETTER INDEX FOR DIAGNOSIS OF VASCULITIS)

LABORATORY IMMUNOLOGY AND KIDNEY TRANSPLANTATION

P.L. Zhang¹, M.A. Farinola², D. Samarapungavan², M.T. Rooney³, S.K. Hicks², S.R. Cohn², G.H. Reddy², L.L. Rocher², F. Dumler², R.K. Parasuraman^2
1Anatomic Pathology, Nephrology And Transplantation, William Beamont Hospital, Royal Oak/UNITED STATES OF AMERICA, ²Anatomic Pathology, Nephrology And Transplantation, William Beaumont Hospital, Royal Oak/UNITED STATES OF AMERICA, ³Anatomic Pathology, Nephrology And Transplantation, William Beaumont Hospital, Royal Oak/MI/UNITED STATES OF AMERICA

Body: Introduction. The Banff criteria (from 2005 to 2009) use "T cell mediated rejection" to indicate acute cellular rejection. Vasculitis in smaller arteries is an important diagnostic criterion for moderate and severe "T cell mediated rejection". The renal allograft endothelium is a significant target of inflammatory response mediated tissue damage. Medium size arteries (arcuate arteries) are mostly absent in routine allograft biopsies, so identification of vasculitis relies on its identification in small arteries (arterioles to interlobar arteries). Although inflammation in terminal vessels such as the glomerular capillaries has been previously recognized, their role in grading the rejection process is not well characterized. We therefore evaluated the expression of CD3 positive T lymphocytes and CD68 positive macrophages in glomeruli, small arteries and arcuate arteries of nephrectomy specimens obtained from transplant and renal tumor patients. Methods. The study group included 21 renal explant subjects with non-reversible moderate to severe cellular rejection (IIa to III) and/or severe chronic allograft nephropathy. The control group comprised 17 individuals with nephrectomy for renal tumors. In each case, a large renal section from cortex to medulla was stained for CD3 and CD68 by immunohistochemical method. CD3 positive T lymphocytes and CD68 positive macrophages per balanced high power field (BHPF) were counted in glomeruli, interlobar and arcuate arteries. Results. In control kidney sections, neither CD3 positive T lymphocytes nor CD68 positive macrophages were noted in glomeruli, interlobar arteries or arcuate arteries. In the study group, 15/21 study cases had antibody mediated rejection. Also in the study group, positive CD3 counts in glomeruli were significantly correlated to both interlobar and arcuate artery counts by linear regression analysis (r and p values are listed in the Table 1) as T lymphocyte and macrophage counts are also presented in the table for the three areas studied.

Table 1	T cells (#/BHPF)	r and p vs glomeruli	Macrophages (#/BHPF)	r and p vs glomeruli
Interlobar Arteries	8.7 ± 1.7	0.61; 0.003	10.8 ± 1.2	0.57; 0.007
Arcuate Arteries	8.9 ± 0.9	0.54; 0.012	10.0 ± 0.7	0.44; 0.045
Glomeruli	13.6 ± 2.2	-	11.2 ± 0.6	-

Conclusion. We conclude that in renal allograft biopsies, T lymphocytes and macrophages in the glomeruli not only represent a separate entity “transplant glomerulitis”, but also may be a surrogate marker of vasculitis present in larger vascular beds. Comparable amounts of T cells and macrophages imply that “acute cellular rejection” may be a better terminology to reflect the true inflammatory status than “T-cell mediated rejection”.

Disclosure: All authors have declared no conflicts of interest.