Clinical diagnoses of AID and genetic analysis
FMF , CAPS , TRAPS  and AOSD [4, 5] were diagnosed by clinical AID experts, according to the previously published classification criteria. Patients with non-classified AID, treatment-refractory gout, pleuro-pericarditis, Schnitzler’s syndrome, idiopathic AA amyloidosis and other rare diseases according to expert opinion were also included in this registry. Patients with the clinical diagnosis of a monogenetic AID were screened for variants in MEFV (FMF), NLRP3 (CAPS) and TNFRSF1A (TRAPS). Genetic analyses were conducted at several commercial laboratories.
Single nucleotide polymorphisms (SNP) with a minor allele frequency (MAF) of ≥ 1% in the general population were considered as a variant of unknown significance (VUS) or as benign variant. The Infevers database [13, last access 04 Jan 2021] served as a reference to evaluate the functional role of single variants. The nomenclature of genetic variants followed the current guidelines of the Human Genome Organisation (HUGO), Human Genome Nomenclature Committee (HGNC), Human Genome Variation Society (HGVS) and the Infevers database . The MAF was derived from the National Center for Biotechnology Information (NCBI) SNP data base (https://www.ncbi.nlm.nih.gov/pubmed).
The MEFV variant p.Arg202Gln (R202Q, rs224222, MAF 0.136) was considered as benign polymorphism. The MEFV variants p.Glu148Gln (E148Q, rs3743930, MAF 0.126), p.Gln230Lys (E230K, rs104895080, MAF 0.00001), p.Pro369Ser (P369S, rs11466023, MAF 0.02), p.Arg408Gln (R408Q, rs11466023, MAF 0.02), p.Ile591Thr (I591T, rs11466045, MAF 0.004) and p.Ala744Ser (A744S, rs61732874, MAF 0.002) were considered as VUS. The MEFV variants p.Phe479Leu (F479L, rs104895083, MAF 0.00001), p.Met680Ile (M680I, rs28940580, MAF 0.00006), p.Met694Val (M694V, rs61752717, MAF 0.0002), p.Lys695Arg (K695R, rs104895094, MAF 0.002), p.Val726Ala (V726A, rs28940579, MAF 0.0002) and p.Arg761His (R761H, rs104895097, MAF 0.0002) were considered as pathogenic MEFV variants.
NLRP3 variants p.Arg137His (R135H, rs138946894 MAF 0.0002), p.Val200Met (V198M, rs121908147, MAF 0.004), p.Leu362Gln (L360Q, unknown), p.Arg490Lys (R488K, rs145268073, MAF 0.0002), p.Arg556Leu (R554L, unknown), p.Phe581Tyr (F579Y, unknown), p.Pro651Ser (P649S, unknown) and p.Gln705Lys (Q703K, rs35829419, MAF 0.02) were considered as VUS. Pathogenic NLRP3 variants were p.Arg262Trp (R260W, rs121908150), p.Asp305Asn (D303N, 121908153), p.Thr350Met (T348M, rs151344629), p.Ala441Val (A439V, rs121908146) and p.Gly571Arg (G569R, rs121908151).
The TNFRSF1A variant p.Arg121Gln (R92Q, rs4149584; MAF 0.006) was considered as VUS. Pathogenic TNFRSF1A variants were p.Tyr49Cys (Y20C; unknown), p.Tyr49His (Y20H; unknown), p.Cyc84Arg (C55R; unknown), p.Thr79Met (T50M; rs104895219) and p.Ile199Asn (I170N; unknown).
Anti-IL1 targeted medication:
AKN was initiated using 100mg sc daily. Patients with renal failure started with AKN 100mg sc 3 times a week. Patients with severe local reactions to AKN reduced their schedule to AKN every 2 to 3 days until local reactions disappeared. Patients with partial control of the attacks used AKN 100mg bid during an attack and 100mg every day for maintenance.
CAN was initiated using 150mg sc. every 8 weeks. Patients with a transient response for 4 to 8 weeks reduced the intervals to 150mg every 4 weeks. Patients with a partial response to 150mg used CAN 300mg every 4 to 8 weeks to maximize the response and to achieve remission.
Some patients who had an inadequate response or intolerance to AKN were switched to CAN.