Chronic intestinal graft-versus-host disease: clinical, histological and immunohistochemical analysis of 17 children

Abstract

Graft-versus-host disease (GVHD) can be acute or chronic. The pathogenesis of chronic GVHD is unclear. Chronic GVHD affects mainly skin, liver and digestive tract. Intestinal involvement is uncommon and histological features are poorly described. We report here the clinical, histological and immunohistochemical features of chronic GVHD with intestinal involvement. Intestinal biopsies from children with chronic GVHD (n = 17) were compared to control children (n = 21: 10 non-transplant cases, four non-GVHD transplant cases, seven acute GVHD). We evaluated clinical outcome, histological features and characterized immunohistochemically the immune cells involved locally. Chronic GVHD with intestinal involvement was usually multisystemic (88.2%) and preceded by acute GVHD in 88.2% of cases. The outcome was severe with complete recovery in only 58.8% of cases, and death related to chronic GVHD in 17.6% of cases. Histological features were characterized by (1) villous atrophy and (2) glandular lesions, mainly apoptotic with variable intensity and (3) lamina propria infiltrate with cytotoxic T lymphocytes (CD3 + , CD8 + , TiA1 + , granzyme B −) which were significantly (P Ͻ 0.001) increased compared to non-GVHD transplant and non-transplant controls. Therefore in chronic intestinal GVHD, the apoptotic process could be related to cytotoxic T lymphocytes.

Digestive histopathological presentation of IPEX syndrome

“…5, 6, 7, 8 and 9). The morphological aspect of these apoptotic lesions is indistinguishable from those observed in classical intestinal graft-vs-host disease 13,14 (Figure 1b, inset). In addition, lymphocytic, neutrophilic and eosinophilic infiltration of the epithelium crypts, with crypt abscesses, was always present.…”

Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease

“…31,32 CD3 ϩ CD8 ϩ cytolytic T cells are important effector cells in both acute and chronic GVHD. [33][34][35][36][37][38][39] In our studies, the frequency of CD3 ϩ CD8 ϩ cells in PBLs was inversely correlated with the frequency of CD4 ϩ CD25 ϩ cells, suggesting a direct physiologic relation between Tregs and CTLs. This association might reflect the balance of the posttransplant immune response tipping between 2 extremes: increased Tregs associated with decreased cytolytic effector T cells, corresponding to a controlled immune response, or decreased Tregs associated with larger numbers of CTLs, resulting in escalating immune responses.…”

Immunohistochemical and FISH analyses identify synovitis associated with chronic GVHD after allogeneic hematopoietic SCT

“…5,6 A preponderance of CD8 þ /TIA-1 þ cytotoxic lymphocytes has been described in intestinal cGVHD specimens. 7 Similarly, in conjunctival cGVHD, CD8 þ /CD25 þ /TIA-1 þ /HLA-DR þ cells were found increased. 8 In our synovial tissue, we found a few CD4 þ /CD25 þ cells, while FoxP3 was negative.…”