Immune dysregulation diseases comprise a group of disorders that can trigger defective or uncontrolled immune responses and are characterized by autoimmunity, episodes of recurrent autoinflammation, dysregulation of lymphocyte homeostasis, or hypersensitivity reactions. These disorders are caused by distinct genetic defects, some of which can also cause immunodeficiency. Prevalence varies between 1:5,000 and 1:100,000 for some diseases. The complexity and symptom overlap makes genetic testing essential for the understanding of the disease, the diagnosis, and anticipation of disease behaviour and patient management.
Immune dysregulation disorders (IDD) comprise a group of disorders that can be clinically and biologically distinguished from primary immunodeficiencies. They are caused by distinct genetic defects in immune regulatory pathways, some of which can also cause immunodeficiency. This group of diseases do not usually show depletion of the cellular or humoral immunity, but immune response sensors are defective or uncontrolled, which manifests as a loss of immune tolerance or recurrent inflammation. Environmental factors and aging may contribute to the development of immune dysregulation. The panel is subdivided into autoimmune (adaptive immune system involvement) and autoinflammatory (innate immune system involvement) diseases.
These conditions are characterized by autoimmunity, episodes of recurrent autoinflammation, dysregulation of lymphocyte homeostasis, or hypersensitivity reactions. Immunodeficiency may also be present
The percentage of IDD caused by genetic alterations is undetermined, but the prevalence of phenotypes included in this group could vary between 1:5,000 and 1:100,000 for some diseases. In addition, some genetic factors can contribute to the risk of developing systemic lupus eritematous (SLE) or inflammatory bowel disease (IBD).
The rise in the prevalence of these disorders and the discovery of new genetic causes in recent decades underline the need for precise genetic evaluation. Accurate diagnosis can be followed by a specific treatment, which is critical for patient management.
ABCB1, ACP5, ADA2, ADAM17, ADAR, ADGRE2, AIRE, ANXA11, AP3B1, AP3D1, APOL1, ARID5B, ARPC1B, ATG16L1, ATG5, BANK1, BLK, BTNL2, C1QA, C1QB, C1QC, C1QTNF4, C1R, C1S, C2, C3, C4A, C4B, CALCOCO2, CARD14, CARD9, CARMIL2, CASP10, CASP8, CCDC88B, CCL2, CCL22, CCR1, CCR3, CCR5, CCR9, CD14, CD226, CD27, CD40, CD46, CD55, CD70, CFB, CFH, CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, CFI, CIITA, CLEC16A, CR2, CSK, CTLA4, CTPS1, CXCL13, CXCR5, CYBB, DDX58, DGAT1, DNASE1, DNASE1L3, DNMT3A, DOCK8, E2F1 , EGFR, EPCAM, ERAP1, ETS1, FAAP24, FADD, FAS, FASLG, FCGR2A, FCGR2B, FOXP3, FUT2, GUCY2C, HAS2, HNF1A, ICAM1, ICOS, IFIH1, IKZF1, IKZF3, IL10, IL10RA, IL10RB, IL12A, IL12B, IL12RB1, IL12RB2, IL15, IL15RA, IL18R1, IL1RN, IL23A, IL23R, IL2RA, IL36RN, IL7R, IRAK1, IRF1, IRF2BP2, IRF5, IRF7, IRF8, IRGM, ISG15, ITCH, ITGAM, ITK, KIRREL2, KLRC4, KRAS, LACC1, LAT, LCK, LIMK2, LPIN2, LRBA, LYST, MAGT1, MAN2B1, MASP2, MBL2, MC2R, MCM4, MECP2, MEFV, MICA, MICB, MME, MRAP, MST1, MTHFR, MTMR3, MVK, MYH9, MYO5A, MYO5B, NCF1, NCF2, NEIL1, NEUROG3, NFAT5 , NFKB1, NFKBIA, NLRC4, NLRP12, NLRP3, NOD2, NPHS1, NR0B1, NR4A2, NRAS, OAS1, OAS2, OTULIN, PBX1, PDCD1, PDGFRA, PEPD, PLA2R1, PLCG2, PRDM1, PRF1, PRKCD, PRKG1, PSMB8, PSTPIP1, PTEN, PTGS2, PTPN2, PTPN22, PTPRC, PXK, RAB27A, RAG2, RASGRP1, RBCK1, RECQL4, REL, RNASEH2A, RNASEH2B, RNASEH2C, SAA1, SAMHD1, SATB1, SH2D1A, SKIV2L, SLC26A3, SLC7A7, SLC9A3, SPATA5, SPINT2, STAT1, STAT3, STAT4, STAT5B, STAT6, STK4, STX11, STXBP2, TAGAP, TAP1, TBX21, TCF7, TGFB1, THBD, THBS1, THSD7A, TLR5, TLR7, TLR8, TLR9, TMEM173, TNF, TNFAIP3, TNFRSF11A, TNFRSF13B, TNFRSF1A, TNFRSF4, TNFSF15, TNFSF4, TNIP1, TREX1, TRIM21, TRNT1, TTC37, TTC7A, TYK2, UBAC2, UBE2L3, UHRF1BP1, UNC13D, WDR1, XIAP, XKR6, ZAP70