Perforin gene defects in familial hemophagocytic lymphohistiocytosis

Science

Volumn 286, Issue 5446, 1999, Pages 1957-1959

  Stepp, Susan E ^a   Dufourcq Lagelouse, Rémi ^b   Le Deist, Françoise ^b,c   Bhawan, Sadhna ^a   Certain, Stéphanie ^b   Mathew, Porunelloor A ^d   Henter, Jan Inge ^e   Bennett, Michael ^a   Fischer, Alain ^b,c   De Saint Basile, Geneviève ^b   Kumar, Vinay ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b INSERM   (France)

^c HÔPITAL NECKER ENFANTS MALADES   (France)

^d UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER   (United States)

^e KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

PERFORIN;

ARTICLE; AUTOSOMAL RECESSIVE DISORDER; CHROMOSOME 10Q; CHROMOSOME 9Q; CONTROLLED STUDY; FAMILIAL DISEASE; GENETIC DISORDER; GENETIC LINKAGE; HEMOPHAGOCYTIC SYNDROME; HUMAN; HUMAN CELL; IMMUNOPATHOLOGY; MISSENSE MUTATION; NONSENSE MUTATION; PRIORITY JOURNAL; T LYMPHOCYTE ACTIVATION;

ANTIGEN-PRESENTING CELLS; CELL DEATH; CELL LINE; CELLS, CULTURED; CHROMOSOME MAPPING; CHROMOSOMES, HUMAN, PAIR 10; CODON, TERMINATOR; CYTOPLASMIC GRANULES; CYTOTOXICITY, IMMUNOLOGIC; FRAMESHIFT MUTATION; GRANZYMES; HETEROZYGOTE; HISTIOCYTOSIS, NON-LANGERHANS-CELL; HUMANS; LINKAGE (GENETICS); LYMPHOCYTE ACTIVATION; MEMBRANE GLYCOPROTEINS; MUTATION, MISSENSE; POINT MUTATION; PORE FORMING CYTOTOXIC PROTEINS; SERINE ENDOPEPTIDASES; T-LYMPHOCYTES, CYTOTOXIC;

EID: 0033520970     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.286.5446.1957     Document Type: Article

References (32)

1. J. I. Henter, M. Arico, G. Elinder, S. Imashuku, G. Janka, Hematol. Oncol. Clin. N. Am. 12, 417 (1998).
2. B. E. Favara, Semin. Diagn. Pathol. 9, 63 (1992).
3. M. Arico et al., Leukemia 10, 197 (1996).
4. R. M. Egeler, R. Shapiro, B. Loechelt, A. Filipovich, J. Pediatr. Hematot. Oncol. 18, 340 (1995).
5. K. E. Sullivan, C. A. Delaat, S. D. Douglas, A. H. Filipovich, Pediatr. Res. 44, 465 (1998).
6. J. I. Henter, A. Ehrnst, J. Andersson, G. Elinder, Acta Paediatr. 82, 369 (1993).
7. M. P. Hoang, D. B. Dawson, Z. R. Rogers, R. H. Scheuermann, B. B. Rogers, Hum. Pathol. 29, 1074 (1998).
8. T. M. Fink et al., Genomics 13, 1300 (1992).
9. R. Dufourcq-Lagelouse et al., Am. J. Hum. Genet. 64, 172 (1999).
10. M. Ohadi et al., Am. J. Hum. Genet. 64, 165 (1999).
11. D. Binder et al., J. Exp. Med. 187, 1903 (1998).
12. M. Matloubian et al., J. Virol. 73, 2527 (1999).
13. D. Kagi et al., Science 265, 528 (1994).
14. B. Fadeel, S. Orrenius, J. I. Henter, Br. J. Haematol. 106, 406 (1999).
15. To determine the status of the Fas-/FasL pathway of killing, we cultured peripheral blood cells from a control and two patients (P11 and P25) as described in text. Because anti-CD3-mediated apoptosis depends on Fas-FasL interactions, control and patients cells were incubated on plate-bound (1 μg/ml) OKT3 antibody for 24 hours. Cell death was determined as described (28) and was equivalent in all three samples (range from 55 to 60%). In addition, the cells were incubated with monoclonal anti-Fas (Apo-1) (250 to 0.25 ng/ml) and a rat antibody to mouse immunoglobulin G (IgG) for 24 hours. Fas-mediated apoptosis was present in both control and patient cells. Percentage of apoptotic cells ranged from 5 to 15% at 0.25 ng/ml and 65 to 80% at 250 ng/ml of antibody.
16. M. von Herrath, B. Coon, D. Homann, T. Wolfe, L. G. Guidotti, J. Virol. 73, 5918 (1999).
17. A. Gallimore et al., J. Exp. Med. 187, 1383 (1998).
18. D. Spaner, K. Raju, B. Rabinovich, R. G. Miller, J. Immunol. 162, 1192 (1999).
19. S. Sambhara et al., Cell. Immunol. 187, 13 (1998).
20. S. L. Peng, J. Moslehi, M. E. Robert, J. Craft, J. Immunol. 160, 652 (1998).
21. J. Spielman, R. K. Lee, E. R. Podack, J. Immunol. 161, 7063 (1998).
22. S. M. Gilbertson, P. D. Shah, D. A. Rowley, J. Immunol. 136, 3567 (1986).
23. S. C. Knight, B. A. Askonas, S. E. Macatonia, Adv. Exp. Med. Biol. 417, 389 (1997).
24. A. B. Geldhof, M. Moser, L. Lespagnard, K. Thielemans, P. De Baetselier, Blood 91, 196 (1998).
25. P. Borrow, C. F. Evans, M. B. Oldstone, J. Virol. 69, 1059 (1995).
26. D. Spaner, K. Raju, L. Radvanyi, Y. Lin, R. G. Miller, J. Immunol. 160, 2655 (1998).
27. J. Landman-Parker, F. Le Deist, A. Blaise, O. Brison, A. Fischer, Br. J. Haematol. 85, 37 (1993).
28. F. Rieux-Laucat et al., Science 268, 1347 (1995).
29. G. H. Fisher et al., Cell 81, 935 (1995).
30. Perforin has three exons, and the coding region of the gene was PCR amplified from exon 2 and exon 3. Primers used for amplification were as follows: for exon 2, forward (F2) 5′-CCCTTCCATGTGCCCTGATAATC-3′ and reverse (R2) 5′-AGCAGCCTCCAAGTTTGATTGG-3′; and for exon 3, forward (F3) 5′-CCAGTCCTAGTTCTGCCCACTTAC-3′ and reverse (R3) 5′-GAACCCCTTCAGTCCAAGCATAC-S′. Three to five independent PCR reactions were sequenced for each patient sample with the previously listed primers and the additional forward 5′-CAGGTCAACATAGGCATCCACG-3′ and reverse 5′-TTGCATCTCACCTCATGGGAAC-3′ primers.
31. F. Le Deist, unpublished data.
32. We thank Y. Goureau for confocal analysis; R. Winkler-Pickett and J. Ortaldo for technical help; R. McFarland for discussion; B. Stewart for assistance with figures; and P. V. Sivakumar, J. Schatzle, N. Williams, and M. Seigelman for critical reading of the manuscript. This work was supported by grants from NIH (to V.K. and M.B.) and by grants from the Institut National de la Santé et de la Recherche Médicale and the Association Française Contre les Myopathies (to G.S.B.)