Phenocopies of primary immunodeficiency
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Immunodeficiency Main Page |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ali Akram, M.B.B.S.[2], Anmol Pitliya, M.B.B.S. M.D.[3]
Overview
Classification
| Phenocopies of PID | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Associated with Somatic Mutations | Associated with Auto-Antibodies | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ALPS-SFAS | Chronic mucocutaneous candidiasis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| RALD(RAS-associated autoimmune leukoproliferative disease) | Adult-onset immunodeficiency with susceptibility to mycobacteria | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cryopyrinopathy(Muckle-Wells Syndrome) | Recurrentt skin infections | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypereosinophilic syndrome due to somatic mutations in STAT5b | Pulmonary alveolar proteinosis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Acquired angiooedema | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Atypical Hemolytic Uremic Syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Thymoma with hypogammaglobulinemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ALPS-SFAS
- Heritable disorder of apoptosis, resulting in the accumulation of autoreactive lymphocytes.[1]
- Manifests in early childhood as nonmalignant lymphadenopathy with hepatosplenomegaly and autoimmune cytopenias.[1]
- Patients with mutations have developed B and T-cell lymphomas.[2]
- Peripheral blood analysis in patients has demonstrated hypergammaglobulinemia along with increased numbers of B and T lymphocytes.[3]
- Some studies have demonstrated that ALPS is compatible with long-term survival.[4][5]
Types of mutation
- Type IA is caused by heterozygous mutation in the FAS gene (TNFRSF6, or CD95)
- Type Ib is caused by heterozygous mutation in the FAS ligand (FASL) gene (TNFSF6 or CD95L)
RALD(RAS-associated autoimmune leukoproliferative disease)
- Originally considered a subtype of RAS due to the significant overlap.[6][7]
- A leukoproliferative disorder characterized by lymphadenopathy, splenomegaly, and variable autoimmune phenomena, including autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, and neutropenia.[6][7]
- Some patients have recurrent infections with increased risk of hematologic malignancy.[6][7]
Mutated genes
- NRAS and KRAS
Cryopyrinopathy(Muckle-Wells Syndrome)
- Caused by heterozygous mutation in the gene encoding cryopyrin (NLRP3) and the locus identified at chromosome 1q44.[8][9]
- Characterized by episodic skin rash, arthralgias, and fever associated with late-onset sensorineural deafness and renal amyloidosis.[10]
- Limb pains emphasized on as a feature.[11]
Hypereosinophilic syndrome due to somatic mutations in STAT5b
- Characterized by atopic dermatitis, urticarial rash, diarrhea and eosinophilia
References
- ↑ 1.0 1.1 Dowdell KC, Niemela JE, Price S, Davis J, Hornung RL, Oliveira JB; et al. (2010). "Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome". Blood. 115 (25): 5164–9. doi:10.1182/blood-2010-01-263145. PMC 2892951. PMID 20360470.
- ↑ Straus SE, Jaffe ES, Puck JM, Dale JK, Elkon KB, Rösen-Wolff A; et al. (2001). "The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis". Blood. 98 (1): 194–200. PMID 11418480.
- ↑ Sneller MC, Straus SE, Jaffe ES, Jaffe JS, Fleisher TA, Stetler-Stevenson M; et al. (1992). "A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease". J Clin Invest. 90 (2): 334–41. doi:10.1172/JCI115867. PMC 443107. PMID 1386609.
- ↑ Drappa J, Vaishnaw AK, Sullivan KE, Chu JL, Elkon KB (1996). "Fas gene mutations in the Canale-Smith syndrome, an inherited lymphoproliferative disorder associated with autoimmunity". N Engl J Med. 335 (22): 1643–9. doi:10.1056/NEJM199611283352204. PMID 8929361.
- ↑ Canale VC, Smith CH (1967). "Chronic lymphadenopathy simulating malignant lymphoma". J Pediatr. 70 (6): 891–9. PMID 4165068.
- ↑ 6.0 6.1 6.2 Oliveira JB (2013). "The expanding spectrum of the autoimmune lymphoproliferative syndromes". Curr Opin Pediatr. 25 (6): 722–9. doi:10.1097/MOP.0000000000000032. PMC 4435794. PMID 24240292.
- ↑ 7.0 7.1 7.2 Niemela JE, Lu L, Fleisher TA, Davis J, Caminha I, Natter M; et al. (2011). "Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis". Blood. 117 (10): 2883–6. doi:10.1182/blood-2010-07-295501. PMC 3062298. PMID 21079152.
- ↑ Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD (2001). "Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome". Nat Genet. 29 (3): 301–5. doi:10.1038/ng756. PMC 4322000. PMID 11687797.
- ↑ Cuisset L, Drenth JP, Berthelot JM, Meyrier A, Vaudour G, Watts RA; et al. (1999). "Genetic linkage of the Muckle-Wells syndrome to chromosome 1q44". Am J Hum Genet. 65 (4): 1054–9. doi:10.1086/302589. PMC 1288238. PMID 10486324.
- ↑ Dodé C, Le Dû N, Cuisset L, Letourneur F, Berthelot JM, Vaudour G; et al. (2002). "New mutations of CIAS1 that are responsible for Muckle-Wells syndrome and familial cold urticaria: a novel mutation underlies both syndromes". Am J Hum Genet. 70 (6): 1498–506. PMC 379138. PMID 11992256.
- ↑ Black JT (1969). "Amyloidosis, deafness, urticaria, and limb pains: a hereditary syndrome". Ann Intern Med. 70 (5): 989–94. PMID 5769632.