Dianzani Autoimmune Lymphoproliferative Disease

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

SPP1, APCS, IL17A, SH2D1A, TIMP1, IL17F, UNC13D

Drugs

Allogeneic multi-virus specific T lymphocytes targeting BK virus, cytomegalovirus, human herpesvirus-6, Epstein Barr virus and adenovirus, haematopoietic stem cells and blood progenitors umbilical cord-derived expanded with (1R, 4R)-N1-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)cyclohexane-1,4-diamine dihydrobromide dihydrate

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Clinical Features

Dianzani et al. (1997) identified 6 unrelated patients with a clinical picture resembling that of autoimmune lymphoproliferative syndrome (ALPS; 601859), but the patients showed no expansion of CD4 (186940)/CD8 (see 186910) double-negative T cells. T cells displayed reduced FAS (134637) capacity to induce programmed cell death, but no mutations of the FAS gene were identified. However, the FAS defect seemed to involve the FAS signaling pathway because ceramide, a second messenger for FAS signaling, did not overcome the programmed cell death defect.

Ramenghi et al. (2000) assessed the inherited component of the Dianzani form of autoimmune lymphoproliferative disease by evaluating FAS- and ceramide-induced T-cell death in both parents and 4 close relatives of 10 unrelated patients with the disorder. Most of them (22 of 24) displayed defective FAS- or ceramide-induced (or both) cell death. Moreover, analysis of the family histories showed that frequencies of autoimmunity and cancer were significantly increased in the paternal and maternal line, respectively. Defective FAS- or ceramide-induced T-cell death was also detected in 9 of 17 autoimmune patients from 7 families displaying more than a single case of autoimmunity within first- or second-degree relatives, examples of the multiple autoimmune syndrome (MAS). Autoimmune disease as displayed by the Dianzani syndrome patients and the MAS families included several organ-specific and systemic forms. Ramenghi et al. (2000) interpreted their findings as indicating that the Dianzani form of autoimmune lymphoproliferative disease is due to accumulation of several defects in the same subject and that these defects predispose to development of cancer or autoimmune diseases other than ALPS or the Dianzani syndrome.

Molecular Genetics

Clementi et al. (2006) identified the ala91-to-val (A91V; 170280.0011) substitution in the PRF1 gene in 6 of 28 DALD patients. Presence of A91V conferred an odds ratio of 3 for DALD, and the odds ratio increased to 17 if variations in the osteopontin (SPP1; 166490) gene associated with increased osteopontin production were also present. However, A91V was relatively frequent (4.6%) in controls. Clementi et al. (2006) suggested that A91V may be a susceptibility factor for DALD in patients with defective FAS function.

Nomenclature

Although Dianzani et al. (1997) referred to this condition as autoimmune lymphoproliferative disease with the symbol ALD, these seem to be unsatisfactory designations because the name is too similar to the autoimmune lymphoproliferative syndrome (ALPS) and the symbol has already been used for adrenoleukodystrophy.