0
November 1993, Vol 147, No. 11 >
Article | November 1993

X-linked Lymphoproliferative Disease FREE

Thomas A. Seemayer, MD, FRCPath; Helen Grierson, PhD; Samuel J. Pirruccello, MD; Thomas G. Gross, MD, PhD; Dennis D. Weisenburger, MD; Jack Davis, MT(ASCP); Karen Spiegel; Beda Brichacek, PhD; Janos Sumegi, MD, PhD
[+] Author Affiliations

Accepted for publication July 1, 1993.

Reprint requests to 600 S 42nd St, Omaha, NE 68198-3135 (Dr Seemayer).


Am J Dis Child. 1993;147(11):1242-1245. doi:10.1001/archpedi.1993.02160350116018.
Text Size: A A A
Published online
Article
References
Comments

In 1975, Purtilo et al1 described a fatal X-linked condition that affected boys in the Duncan kindred. The investigators surmised correctly that the disease stemmed from a genetic inability to mount an effective immune response to the Epstein-Barr virus (EBV). This discovery was particularly novel for it represented the first genetically determined immunodeficiency characterized by a selective vulnerability to a specific virus. The condition is now known as X-linked lymphoproliferative (XLP) disease. This article provides an overview of XLP and describes the function of The XLP Registry, founded by David T. Purtilo, MD, in 1978.

THE EPSTEIN-BARR VIRUS  The EBV, one of six known human herpesviruses, has strong trophism for B lymphocytes. In vitro, B cells are infected, immortalized polyclonally, and induced to produce immunoglobulins.2 In vivo, the virus also infects and replicates in the salivary glands and oropharyngeal epithelial cells.3 From these latter sites, it

REFERENCES

1 +
Purtilo DT, Cassel CK, Yang JPS, et al.  X-linked recessive progressive combined variable immunodeficiency (Duncan's disease) . Lancet . 1975;;1: 935-941.
2 +
Rosen A, Gergely P, Jondal M, Klein G, Britton S.  Polyclonal lg production after Epstein-Barr virus infection of human lymphocytes in-vitro . Nature . 1977;;267:52-56.
3 +
Sixbey JW, Nedrud JG, Raab-Traub N, Hanes RA, Pagano JS.  Epstein-Barr virus replication in oropharyngeal epithelial cells . N Engl J Med . 1984;; 310:1225-1230.
4 +
Chang RS, Lewis JP, Abildgaard CF.  Prevalence of oropharyngeal excretors of leukocyte-transforming agents among a human population . N Engl J Med . 1973;;289:1325-1329.
5 +
Epstein MA, Achong BG, Barr YM.  Virus particles in cultured lymphoblasts from Burkitt's lymphoma . Lancet . 1964;;1:702-703.
6 +
Gregory CD, Dive C, Henderson S, et al.  Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis . Nature . 1991;;349:612-615.
7 +
Klein G.  Lymphoma development in mice and humans: diversity of initiation is followed by convergent cytogenetic evolution . Proc Natl Acad Sci U S A . 1979;;76:2442-2446.
8 +
zur Hausen H, Schulte-Holthausen H, Klein G, et al.  EBV DNA in biopsies of Burkitt's tumors and anaplastic carcinoma of the nasopharynx . Nature . 1970;;228:1056-1058.
9 +
Hanto DW, Gajl-Peczalska KG, Kazimiera J, et al.  Epstein-Barr virus (EBV)-induced polyclonal and monoclonal lymphoproliferative diseases occurring after renal transplantation . Ann Surg . 1983;;198:356-369.
10 +
Okano N, Thiele GM, Davis JR, Grierson H, Purtilo DT.  Epstein-Barr virus and human diseases: recent advances in diagnosis . Clin Microbiol Rev . 1988;;1:300-312.
11 +
Shearer WT, Ritz J, Finegold M, et al.  Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency . N Engl J Med . 1985;;312:1151-1159.
12 +
Borisch-Chappuis B, Müller H, Stutle J, Hey MM, Hübner K, Müller-Hermelink HK.  Identification of EBV-DNA in lymph nodes from patients with lymphadenopathy and lymphomas associated with AIDS . Virchows Arch B Cell Pathol . 1990;;58:199-205.
13 +
Brichacek B, Davis J, Purtilo DT.  Presence of monoclonal and oligoclonal B-cell lymphoproliferation in fatal infection mononucleosis . In: Levine PH, Ablashi DV, Nonoyama M, eds. Epstein-Barr Virus and Human Disease . Clifton, NJ: Humana Press; 1987;:53-54.
14 +
Purtilo DT, Strobaugh RS, Okano M, Davis JR.  Biology of disease: Epstein-Barr virus-associated lymphoproliferative disorders . Lab Invest . 1992;;67:5-23.
15 +
Murray R, Kiruilla M, Griffin H, et al.  Human cytotoxic T cell response against Epstein-Barr virus nuclear antigens demonstrated using recombinant vaccinia viruses . Proc Natl Acad Sci U S A . 1990;;87:2906-2910.
16 +
Skare JC, Grierson HL, Sullivan JL, et al.  Linkage analysis of seven kindreds with the X-linked lymphoproliferative syndrome (XLP) confirms that the XLP locus is near DSX42 and DSX47 . Hum Genet . 1989;;82:354-358.
17 +
Grierson HL, Skare JC, Davis JR, et al. Evaluation of families wherein a single male manifests a phenotype of X-linked lymphoproliferative disease (XLP). Am J Med Genet. In press.
18 +
Purtilo DT, Grierson HL, Davis JR, Okano M.  The X-linked lymphoproliferative disease: from autopsy toward cloning the gene, 1975-1990 . Pediatr Pathol . 1991;;11:685-710.
19 +
Purtilo DT, Pacquin LA, DeFlorio D, Virzi F, Shakuja R.  Immunodiagnosis and immunopathogenesis of the X-linked recessive lymphoproliferative syndrome . Semin Hematol . 1979;;16:309-320.
20 +
Purtilo DT.  X-linked lymphoproliferative disease (XLP) as a model of Epstein-Barr virus-induced immunopathology . Springer Semin Immunopathol . 1991;;13:181-197.
21 +
Weisenburger DD, Purtilo DT.  Failure in immunological control of the virus infection: fatal infectious mononucleosis . In: Epstein MA, Schong BG, eds. The Epstein-Barr Virus: Recent Advances . London, England: Heinemann Medical Books; 1986;:129-161.
22 +
Grierson HL, Purtilo DT.  Epstein-Barr virus infections in males with the X-linked lymphoproliferative syndrome . Ann Intern Med . 1987;;106:538-545.
23 +
Harrington DS, Weisenburger DD, Purtilo DT.  Malignant lymphomas in the X-linked lymphoproliferative syndrome . Cancer . 1987;;59:1419-1429.
24 +
Skare JC, Milunsky A, Byron KS, Sullivan JL.  Mapping the X-linked lymphoproliferative syndrome . Proc Natl Acad Sci USA . 1987;;84:2015-2028.
25 +
Wyandt HE, Grierson HL, Sanger WG, Skare JC, Milunsky H, Purtilo DT.  Chromosomal deletion of Xq25 in an individual with X-linked lymphoproliferative disease . Am J Med Genet . 1989;;33:426-430.
26 +
Sanger WG, Grierson HL, Skare J, et al.  Partial Xq25 deletion in a family with the X-linked lymphoproliferative disease (XLP) . Cancer Genet Cytogenet . 1990;;47:163-169.
27 +
Skare J, Wu B-L, Madan S, et al.  Characterization of three overlapping deletions causing X-linked lymphoproliferative disease . Genomics . 1993;;6: 254-255.
28 +
Grierson HL, Skare J, Hawk J, Pauza M, Purtilo DT.  Immunoglobulin class and subclass deficiencies prior to Epstein-Barr virus infection in males with X-linked lymphoproliferative disease . Am J Med Genet . 1991;;40:294-297.
29 +
Purtilo DT, Grierson HL, Ochs H.  Detection of X-linked lymphoproliferative disease (XLP) using molecular and immunovirological markers . Am J Med . 1989;;87:421-424.
30 +
Purtilo DT, Grierson HL.  Methods of detection of new families with X-linked lymphoproliferative disease . Cancer Genet Cytogenet . 1991;;51: 143-153.
31 +
Turner AM, Berdoukas VA, Tobias VA, et al.  Report on the X-linked lymphoproliferative disease in an Australian family . J Pediatr Child Health . 1992;;28:184-189.
32 +
Mulleg JC, Turner AM, Gedeon AK, et al.  X-linked lymphoproliferative disease: prenatal detection of an unaffected histocompatible male . Clin Genet . 1992;;42:76-79.
33 +
Alvarado CS, Buchanan GR, Kim TH, Zaatari G, Sartain P, Ragab AH.  Use of VP-16-213 in the treatment of familial erythrophagocytic lymphohistiocytosis . Cancer . 1986;;57:1097-1100.
34 +
Pracher E, Zoubek A, Peters C, Panzer-Grümayer ER, Mayerhofer L, Gadner H. Successful allogeneic bone marrow transplantation for X-linked lymphoproliferative syndrome (XLP). Presented at the Eighth Annual Meeting of the Histiocyte Society; October 11, 1992; Hanover, Germany.
35 +
Sumegi J, Li S, Li B, et al. Large interstitial deletion in Xq25 observed in two patients occurs infrequently in X-linked lymphoproliferative disease (XLP). Genes Chromosom Cancer. In press.
36 +
Anderson C.  Genome shortcut leads to problems . Science . 1993;;259: 1684-1687.
37 +
Korthäuer U, Graf D, Mages HW, et al.  Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-lgM . Nature . 1993;;361:539-543.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

References

1 +
Purtilo DT, Cassel CK, Yang JPS, et al.  X-linked recessive progressive combined variable immunodeficiency (Duncan's disease) . Lancet . 1975;;1: 935-941.
2 +
Rosen A, Gergely P, Jondal M, Klein G, Britton S.  Polyclonal lg production after Epstein-Barr virus infection of human lymphocytes in-vitro . Nature . 1977;;267:52-56.
3 +
Sixbey JW, Nedrud JG, Raab-Traub N, Hanes RA, Pagano JS.  Epstein-Barr virus replication in oropharyngeal epithelial cells . N Engl J Med . 1984;; 310:1225-1230.
4 +
Chang RS, Lewis JP, Abildgaard CF.  Prevalence of oropharyngeal excretors of leukocyte-transforming agents among a human population . N Engl J Med . 1973;;289:1325-1329.
5 +
Epstein MA, Achong BG, Barr YM.  Virus particles in cultured lymphoblasts from Burkitt's lymphoma . Lancet . 1964;;1:702-703.
6 +
Gregory CD, Dive C, Henderson S, et al.  Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis . Nature . 1991;;349:612-615.
7 +
Klein G.  Lymphoma development in mice and humans: diversity of initiation is followed by convergent cytogenetic evolution . Proc Natl Acad Sci U S A . 1979;;76:2442-2446.
8 +
zur Hausen H, Schulte-Holthausen H, Klein G, et al.  EBV DNA in biopsies of Burkitt's tumors and anaplastic carcinoma of the nasopharynx . Nature . 1970;;228:1056-1058.
9 +
Hanto DW, Gajl-Peczalska KG, Kazimiera J, et al.  Epstein-Barr virus (EBV)-induced polyclonal and monoclonal lymphoproliferative diseases occurring after renal transplantation . Ann Surg . 1983;;198:356-369.
10 +
Okano N, Thiele GM, Davis JR, Grierson H, Purtilo DT.  Epstein-Barr virus and human diseases: recent advances in diagnosis . Clin Microbiol Rev . 1988;;1:300-312.
11 +
Shearer WT, Ritz J, Finegold M, et al.  Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency . N Engl J Med . 1985;;312:1151-1159.
12 +
Borisch-Chappuis B, Müller H, Stutle J, Hey MM, Hübner K, Müller-Hermelink HK.  Identification of EBV-DNA in lymph nodes from patients with lymphadenopathy and lymphomas associated with AIDS . Virchows Arch B Cell Pathol . 1990;;58:199-205.
13 +
Brichacek B, Davis J, Purtilo DT.  Presence of monoclonal and oligoclonal B-cell lymphoproliferation in fatal infection mononucleosis . In: Levine PH, Ablashi DV, Nonoyama M, eds. Epstein-Barr Virus and Human Disease . Clifton, NJ: Humana Press; 1987;:53-54.
14 +
Purtilo DT, Strobaugh RS, Okano M, Davis JR.  Biology of disease: Epstein-Barr virus-associated lymphoproliferative disorders . Lab Invest . 1992;;67:5-23.
15 +
Murray R, Kiruilla M, Griffin H, et al.  Human cytotoxic T cell response against Epstein-Barr virus nuclear antigens demonstrated using recombinant vaccinia viruses . Proc Natl Acad Sci U S A . 1990;;87:2906-2910.
16 +
Skare JC, Grierson HL, Sullivan JL, et al.  Linkage analysis of seven kindreds with the X-linked lymphoproliferative syndrome (XLP) confirms that the XLP locus is near DSX42 and DSX47 . Hum Genet . 1989;;82:354-358.
17 +
Grierson HL, Skare JC, Davis JR, et al. Evaluation of families wherein a single male manifests a phenotype of X-linked lymphoproliferative disease (XLP). Am J Med Genet. In press.
18 +
Purtilo DT, Grierson HL, Davis JR, Okano M.  The X-linked lymphoproliferative disease: from autopsy toward cloning the gene, 1975-1990 . Pediatr Pathol . 1991;;11:685-710.
19 +
Purtilo DT, Pacquin LA, DeFlorio D, Virzi F, Shakuja R.  Immunodiagnosis and immunopathogenesis of the X-linked recessive lymphoproliferative syndrome . Semin Hematol . 1979;;16:309-320.
20 +
Purtilo DT.  X-linked lymphoproliferative disease (XLP) as a model of Epstein-Barr virus-induced immunopathology . Springer Semin Immunopathol . 1991;;13:181-197.
21 +
Weisenburger DD, Purtilo DT.  Failure in immunological control of the virus infection: fatal infectious mononucleosis . In: Epstein MA, Schong BG, eds. The Epstein-Barr Virus: Recent Advances . London, England: Heinemann Medical Books; 1986;:129-161.
22 +
Grierson HL, Purtilo DT.  Epstein-Barr virus infections in males with the X-linked lymphoproliferative syndrome . Ann Intern Med . 1987;;106:538-545.
23 +
Harrington DS, Weisenburger DD, Purtilo DT.  Malignant lymphomas in the X-linked lymphoproliferative syndrome . Cancer . 1987;;59:1419-1429.
24 +
Skare JC, Milunsky A, Byron KS, Sullivan JL.  Mapping the X-linked lymphoproliferative syndrome . Proc Natl Acad Sci USA . 1987;;84:2015-2028.
25 +
Wyandt HE, Grierson HL, Sanger WG, Skare JC, Milunsky H, Purtilo DT.  Chromosomal deletion of Xq25 in an individual with X-linked lymphoproliferative disease . Am J Med Genet . 1989;;33:426-430.
26 +
Sanger WG, Grierson HL, Skare J, et al.  Partial Xq25 deletion in a family with the X-linked lymphoproliferative disease (XLP) . Cancer Genet Cytogenet . 1990;;47:163-169.
27 +
Skare J, Wu B-L, Madan S, et al.  Characterization of three overlapping deletions causing X-linked lymphoproliferative disease . Genomics . 1993;;6: 254-255.
28 +
Grierson HL, Skare J, Hawk J, Pauza M, Purtilo DT.  Immunoglobulin class and subclass deficiencies prior to Epstein-Barr virus infection in males with X-linked lymphoproliferative disease . Am J Med Genet . 1991;;40:294-297.
29 +
Purtilo DT, Grierson HL, Ochs H.  Detection of X-linked lymphoproliferative disease (XLP) using molecular and immunovirological markers . Am J Med . 1989;;87:421-424.
30 +
Purtilo DT, Grierson HL.  Methods of detection of new families with X-linked lymphoproliferative disease . Cancer Genet Cytogenet . 1991;;51: 143-153.
31 +
Turner AM, Berdoukas VA, Tobias VA, et al.  Report on the X-linked lymphoproliferative disease in an Australian family . J Pediatr Child Health . 1992;;28:184-189.
32 +
Mulleg JC, Turner AM, Gedeon AK, et al.  X-linked lymphoproliferative disease: prenatal detection of an unaffected histocompatible male . Clin Genet . 1992;;42:76-79.
33 +
Alvarado CS, Buchanan GR, Kim TH, Zaatari G, Sartain P, Ragab AH.  Use of VP-16-213 in the treatment of familial erythrophagocytic lymphohistiocytosis . Cancer . 1986;;57:1097-1100.
34 +
Pracher E, Zoubek A, Peters C, Panzer-Grümayer ER, Mayerhofer L, Gadner H. Successful allogeneic bone marrow transplantation for X-linked lymphoproliferative syndrome (XLP). Presented at the Eighth Annual Meeting of the Histiocyte Society; October 11, 1992; Hanover, Germany.
35 +
Sumegi J, Li S, Li B, et al. Large interstitial deletion in Xq25 observed in two patients occurs infrequently in X-linked lymphoproliferative disease (XLP). Genes Chromosom Cancer. In press.
36 +
Anderson C.  Genome shortcut leads to problems . Science . 1993;;259: 1684-1687.
37 +
Korthäuer U, Graf D, Mages HW, et al.  Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-lgM . Nature . 1993;;361:539-543.

Correspondence

Submit a Letter
CME
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Clear Answers | Save For Later
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
Submit a Comment

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

© 2013 American Medical Association. All Rights Reserved.
Powered bySilverchair Information Systems