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X-linked Lymphoproliferative Syndrome Differential Diagnoses

  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Nov 26, 2015
Contributor Information and Disclosures

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.


Doris Ponce, MD Fellow, Department of Hematology/Oncology, New York Medical College

Doris Ponce, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Koyamangalath Krishnan, MD, FRCP, FACP Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, Royal College of Physicians

Disclosure: Nothing to disclose.


M Wayne Saville, MD Associate Professor of Clinical Medicine, University of California at San Diego; Director, Hematology and Oncology, Global Medical Affairs, Biogen Idec, Inc

M Wayne Saville, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and Sigma Xi

Disclosure: Nothing to disclose.

  1. Chaganti S, Ma CS, Bell AI, et al. Epstein-Barr virus persistence in the absence of conventional memory B cells: IgM+IgD+CD27+ B cells harbor the virus in X-linked lymphoproliferative disease patients. Blood. 2008 Aug 1. 112(3):672-9. [Medline].

  2. Rigaud S, Fondanèche MC, Lambert N, et al. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature. 2006 Nov 2. 444(7115):110-4. [Medline].

  3. Lankester AC, Visser LF, Hartwig NG, et al. Allogeneic stem cell transplantation in X-linked lymphoproliferative disease: two cases in one family and review of the literature. Bone Marrow Transplant. 2005 Jul. 36(2):99-105. [Medline].

  4. Milone MC, Tsai DE, Hodinka RL, et al. Treatment of primary Epstein-Barr virus infection in patients with X-linked lymphoproliferative disease using B-cell-directed therapy. Blood. 2005 Feb 1. 105(3):994-6. [Medline]. [Full Text].

  5. Sullivan JL. The abnormal gene in X-linked lymphoproliferative syndrome. Curr Opin Immunol. 1999 Aug. 11(4):431-4. [Medline].

  6. Brandau O, Schuster V, Weiss M, et al. Epstein-Barr virus-negative boys with non-Hodgkin lymphoma are mutated in the SH2D1A gene, as are patients with X-linked lymphoproliferative disease (XLP). Hum Mol Genet. 1999 Dec. 8(13):2407-13. [Medline]. [Full Text].

  7. Coffey AJ, Brooksbank RA, Brandau O, et al. Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene. Nat Genet. 1998 Oct. 20(2):129-35. [Medline].

  8. Nichols KE, Harkin DP, Levitz S, et al. Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome. Proc Natl Acad Sci U S A. 1998 Nov 10. 95(23):13765-70. [Medline]. [Full Text].

  9. Purtilo DT, Grierson HL, Davis JR, Okano M. The X-linked lymphoproliferative disease: from autopsy toward cloning the gene 1975-1990. Pediatr Pathol. 1991 Sep-Oct. 11(5):685-710. [Medline].

  10. Harrington DS, Weisenburger DD, Purtilo DT. Malignant lymphoma in the X-linked lymphoproliferative syndrome. Cancer. 1987 Apr 15. 59(8):1419-29. [Medline].

  11. Booth C, Gilmour KC, Veys P, Gennery AR, Slatter MA, Chapel H. X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease. Blood. 2011 Jan 6. 117(1):53-62. [Medline].

  12. Ambrosio MR, Rocca BJ, Ginori A, Mourmouras V, Amato T, Vindigni C, et al. A Look Into the Evolution of Epstein-Barr Virus-Induced Lymphoproliferative Disorders: A Case Study. Am J Clin Pathol. 2015 Nov. 144 (5):817-22. [Medline].

  13. Ma CS, Nichols KE, Tangye SG. Regulation of cellular and humoral immune responses by the SLAM and SAP families of molecules. Annu Rev Immunol. 2007. 25:337-79. [Medline].

  14. Tangye SG, Lazetic S, Woollatt E, et al. Cutting edge: human 2B4, an activating NK cell receptor, recruits the protein tyrosine phosphatase SHP-2 and the adaptor signaling protein SAP. J Immunol. 1999 Jun 15. 162(12):6981-5. [Medline]. [Full Text].

  15. Sayos J, Wu C, Morra M, et al. The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM. Nature. 1998 Oct 1. 395(6701):462-9. [Medline].

  16. Bárcena P, Jara-Acevedo M, Tabernero MD, López A, Sánchez ML, García-Montero AC, et al. Phenotypic profile of expanded NK cells in chronic lymphoproliferative disorders: a surrogate marker for NK-cell clonality. Oncotarget. 2015 Nov 6. [Medline].

  17. Pachlopnik Schmid J, Canioni D, Moshous D, Touzot F, Mahlaoui N, Hauck F, et al. Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency). Blood. 2011 Feb 3. 117(5):1522-9. [Medline].

  18. Marsh RA, Bleesing JJ, Filipovich AH. Using flow cytometry to screen patients for X-linked lymphoproliferative disease due to SAP deficiency and XIAP deficiency. J Immunol Methods. 2010 Oct 31. 362(1-2):1-9. [Medline]. [Full Text].

  19. Marsh RA, Bleesing JJ, Filipovich AH. Flow cytometric measurement of SLAM-associated protein and X-linked inhibitor of apoptosis. Methods Mol Biol. 2013. 979:189-97. [Medline].

  20. Gross TG, Filipovich AH, Conley ME, et al. Cure of X-linked lymphoproliferative disease (XLP) with allogeneic hematopoietic stem cell transplantation (HSCT): report from the XLP registry. Bone Marrow Transplant. 1996 May. 17(5):741-4. [Medline].

  21. Booth C, Gilmour KC, Veys P, Gennery AR, Slatter MA, Chapel H. X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease. Blood. 2011 Jan 6. 117(1):53-62. [Medline].

  22. Gürgey A, Sayli T, Kara A, Kale G, Berkel I. Treatment of X-linked lymphoproliferative disease (Duncan disease) with high-dose methylprednisolone and etoposide (VP-16). Turk J Pediatr. 1996 Apr-Jun. 38(2):217-22. [Medline].

  23. Rivat C, Booth C, Alonso-Ferrero M, Blundell M, Sebire NJ, Thrasher AJ. SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease. Blood. 2013 Feb 14. 121(7):1073-6. [Medline].

  24. Amrolia P, Gaspar HB, Hassan A, et al. Nonmyeloablative stem cell transplantation for congenital immunodeficiencies. Blood. 2000 Aug 15. 96(4):1239-46. [Medline]. [Full Text].

  25. Marsh RA, Madden L, Kitchen BJ, ET AL. XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease. Blood. 2010 May 20. epub ahead of print. [Medline].

  26. Nagy N, Klein E. Deficiency of the proapoptotic SAP function in X-linked lymphoproliferative disease aggravates Epstein-Barr virus (EBV) induced mononucleosis and promotes lymphoma development. Immunol Lett. 2010 May 4. 130(1-2):13-8. [Medline].

  27. Nagy N, Matskova L, Hellman U, Klein G, Klein E. The apoptosis modulating role of SAP (SLAM associated protein) contributes to the symptomatology of the X linked lymphoproliferative disease. Cell Cycle. 2009 Oct 1. 8(19):3086-90. [Medline].

  28. Purtilo DT, Cassel C, Yang JP. Fatal infectious mononucleosis in familial lymphohistiocytosis (letter). N Engl J Med. 1974 Oct 3. 291(14):736. [Medline].

  29. Purtilo DT, Cassel CK, Yang JP, Harper R. X-linked recessive progressive combined variable immunodeficiency (Duncan's disease). Lancet. 1975 Apr 26. 1(7913):935-40. [Medline].

  30. Purtilo DT, DeFlorio D Jr, Hutt LM, et al. Variable phenotypic expression of an X-linked recessive lymphoproliferative syndrome. N Engl J Med. 1977 Nov 17. 297(20):1077-80. [Medline].

  31. Purtilo DT, Yang JP, Allegra S, et al. Hematopathology and pathogenesis of the X-linked recessive lymphoproliferative syndrome. Am J Med. 1977 Feb. 62(2):225-33. [Medline].

  32. Snow AL, Marsh RA, Krummey SM, et al. Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency. J Clin Invest. 2009 Oct. 119(10):2976-89. [Medline]. [Full Text].

  33. Sumegi J, Huang D, Lanyi A, et al. Correlation of mutations of the SH2D1A gene and epstein-barr virus infection with clinical phenotype and outcome in X-linked lymphoproliferative disease. Blood. 2000 Nov 1. 96(9):3118-25. [Medline]. [Full Text].

  34. Tran H, Nourse J, Hall S, et al. Immunodeficiency-associated lymphomas. Blood Rev. 2008 Sep. 22(5):261-81. [Medline].

  35. Veillette A. SLAM-family receptors: immune regulators with or without SAP-family adaptors. Cold Spring Harb Perspect Biol. 2010 Mar. 2(3):a002469. [Medline]. [Full Text].

  36. Williams LL, Rooney CM, Conley ME, et al. Correction of Duncan's syndrome by allogeneic bone marrow transplantation. Lancet. 1993 Sep 4. 342(8871):587-8. [Medline].

  37. Ziegner UH, Ochs HD, Schanen C, et al. Unrelated umbilical cord stem cell transplantation for X-linked immunodeficiencies. J Pediatr. 2001 Apr. 138(4):570-3. [Medline].

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