Occurrence of autoantibodies in chronic graft vs. host disease after allogeneic stem cell transplantation

Wechalekar, AD; Cranfield, Tanya; Sinclair, David; Ganzckowski, M.

doi:10.1111/j.1365-2257.2005.00699.x

Cited by 38 publications

(23 citation statements)

References 10 publications

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“…Consistent with these findings, the presence of antibodies specific for HY proteins were found to correlate with the subsequent development of chronic GVHD (18). Autoantibodies have also been described in patients with chronic GVHD (19,20). An immunopathologic role for B cells in this disease is further emphasized by the observation that treatment with anti-CD20 monoclonal antibody, rituximab, has resulted in clinical improvement in some patients with steroid-resistant chronic GVHD (21 -23).…”

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confidence: 72%

High Levels of B-Cell Activating Factor in Patients with Active Chronic Graft-Versus-Host Disease

Sarantopoulos¹,

Stevenson

Kim

et al. 2007

Clinical Cancer Research

227

180

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Purpose: Recent studies suggest that donor B cells as well as T cells contribute to immune pathology in patients with chronic graft-versus-host disease (GVHD). B-cell activating factor (BAFF) promotes survival and differentiation of activated B cells. Thus, we tested whether BAFF correlated with chronic GVHD disease activity and time of onset after allogeneic hematopoietic stem cell transplantation (HSCT). Experimental Design: Patients who had undergone allogeneic HSCT between 1994 and 2005 for hematologic malignancies were studied. ELISA was used to measure plasma BAFF levels and flow cytometry was used to assess BAFF receptor expression on B cells in patients with or without chronic GVHD. Results: In 104 patients, BAFF levels were significantly higher in patients with active chronic GVHD compared with those without disease (P = 0.02 and 0.0004, respectively).Treatment with high-dose prednisone (z30 mg/d) was associated with reduced BAFF levels in patients with active chronic GVHD (P = 0.0005). Serial studies in 24 patients showed that BAFF levels were high in the first 3 months after HSCT but subsequently decreased in 13 patients who never developed chronic GVHD. In contrast, BAFF levels remained elevated in 11 patients who developed chronic GVHD. Six-month BAFF levels z10 ng/mL were strongly associated with subsequent development of chronic GVHD (P < 0.0001). Following transplant, plasma BAFF levels correlated inversely with BAFF receptor expression on B cells (P = 0.01), suggesting that soluble BAFF affected B cells through this receptor. Conclusion: These results suggest that elevated BAFF levels contribute to B-cell activation in patients with active chronic GVHD.

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confidence: 72%

High Levels of B-Cell Activating Factor in Patients with Active Chronic Graft-Versus-Host Disease

Sarantopoulos¹,

Stevenson

Kim

et al. 2007

Clinical Cancer Research

227

180

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“…In support of a B-cell role (4)(5)(6)(7)(8)(9), the presence of circulating autoantibody (10) and alloantibody (11,12) have been associated with development of cGVHD. Specifically, predominant B-cell subsets have been demonstrated in patients with cGVHD and identified in different studies as naïve (6) and postgerminal center B cells (7,8,10).…”

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confidence: 99%

H–Y antigen-binding B cells develop in male recipients of female hematopoietic cells and associate with chronic graft vs. host disease

Sahaf¹,

Yang

Arai³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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B cells are known to play an important role in pathogenesis of human chronic graft vs. host disease (cGVHD). Our group has previously shown that IgG allo-antibodies recognize Y chromosomeencoded proteins (H-Y) and a dominant H-Y epitope, DEAD box protein (DBY-2) detectable 6-12 mo after transplant in male patients who receive grafts from female donors (F→M) hematopoietic cell transplantation (HCT). Here we present FACS studies of peripheral blood mononuclear cells collected 6 mo after transplant showing that 16 of 28 (57%) F→M HCT patients have circulating donor B cells that express B-cell receptor (mainly IgM and Igλ) specific for DBY-2. The detection of these DBY-2 B cells 6 mo after HCT are associated with cGVHD development (P = 0.004). Specifically, 15 of 16 F→M with DBY-2 B cells developed cGVHD. In contrast, cGVHD developed in only 5 of the 12 who did not have DBY-2 B cells detected. This demonstrates circulating human B cells binding an alloantigen (DBY-2) and that these DBY-2-specific B cells appear before development of cGVHD in roughly half of the F→M patients. Our study suggests that detection of anti-DBY-2 B cells may predict cGVHD and that this prediction may have clinical utility. Validation of this hypothesis will require larger prospective studies.allogeneic | antigen-specific B cells | transplantation | DDX3Y

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“…Chronic GVHD mimics or is associated with various autoimmune diseases (eg, systemic sclerosis, Sjögren syndrome, myasthenia gravis, and polymyositis). [9][10][11] Membranous nephropathy may represent another consequence of this graft-host conflict. 4 On the other hand, there are several case reports of membranous nephropathy after hematopoietic stem cell transplant without chronic GVHD; these suggest the existence of de novo membranous nephropathy after hematopoietic stem cell transplant.…”

Section: Discussionmentioning

confidence: 99%

De Novo Postallogeneic Hematopoietic Stem Cell Transplant Membranous Nephropathy

Numata¹,

Morishita²,

Mori³

et al. 2012

Exp Clin Transplant

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We report membranous nephropathy in a 61-yearold man after allogeneic hematopoietic stem cell transplant without chronic graft-versus-host disease. A diagnosis of acute myeloid leukemia was made, and the patient received hematopoietic stem cell transplants, twice, from different donors. The first donor was his brother and the second donor was an unrelated man.Human leukocyte antigens between donors and recipient were fully matched. His clinical course was stable without acute or chronic graft-versus-host disease or relapse of acute myeloid leukemia with tacrolimus after the second hematopoietic stem cell transplant. Six months after the second hematopoietic stem cell transplant, tacrolimus was decreased gradually and discontinued because of tacrolimus-induced liver dysfunction. Three months after discontinuing the tacrolimus, the patient developed edema in his leg. The results of a blood analysis showed that plasma albumin level was 21 g/L and plasma total cholesterol level was 11.5 mmol/L, while results from a urinalysis showed proteinuria of 5.6 g/d without hematuria. No abnormalities in the skin, mucosal tissues, and other organs suggestive of chronic graft-versus-host disease were seen. A renal biopsy was done to investigate the cause, which revealed renal disease. Electron microscopic analysis showed dense deposits in the subepithelial region in all glomeruli.Immunofluorescence analysis showed the deposition of IgG4 and C3c in the subepithelial space of all glomeruli. Membranous nephropathy was diagnosed. He then was administered prednisolone at a dosage of 45 mg/d (0.7 mg/kg/d). After prednisolone treatment, urine protein and hypoalbuminemia were markedly improved, and his leg edema disappeared.These results suggest that this membranous nephropathy may have been de novo membranous nephropathy after hematopoietic stem cell transplant because it developed after hematopoietic stem cell transplants without chronic graft-versus-host disease.

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Occurrence of autoantibodies in chronic graft vs. host disease after allogeneic stem cell transplantation

Cited by 38 publications

References 10 publications

High Levels of B-Cell Activating Factor in Patients with Active Chronic Graft-Versus-Host Disease

High Levels of B-Cell Activating Factor in Patients with Active Chronic Graft-Versus-Host Disease

H–Y antigen-binding B cells develop in male recipients of female hematopoietic cells and associate with chronic graft vs. host disease

De Novo Postallogeneic Hematopoietic Stem Cell Transplant Membranous Nephropathy

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