Introduction Autoimmune lymphoproliferative syndrome (ALPS) is a rare autosomal immunodeficiency sometimes caused by mutations in 4 genes that affect the extrinsic apoptotic pathway (FAS, FASL, CASP10, CASP8).

Objective This study evaluated patients’ clinical manifestations, laboratory findings and molecular genetic results in 250 patients with a preliminary diagnosis of ALPS.

Methods Annexin expression levels and DNT rates were evaluated by FACs, and results were examined with the Shapiro-Wilk normality test. Normally distributed parameters were compared tested with parametric tests (One Way ANOVA), while abnormal distributions were compared and tested with non-parametric tests (Independent Samples Kruskal Wallis test).

Results Of the 250 patients, 41 met the criteria for definitive ALPS, from which 14 had abnormal Annexin expression rates, 11 equivocal, and 10 normal. 22 of the 250 patients had suspected ALPS, of which only 1 had abnormal Annexin expression rates, 2 equivocal, and 17 normal. Definitive ALPS patients had a significantly lower annexin expression rate than both patients with suspected ALPS and patients not meeting the ALPS criteria (p=,003). The definitive ALPS patient population also showed higher double-negative T-cell levels than those with suspected ALPS or those with no clinical signs. The data shows that patients with FAS mutations are more likely to have low annexin levels than patients with CASP mutations. Regarding the sFASI, definitive ALPS patients showed higher values compared to patients with no ALPS or suspected ALPS (median sFASI: 186,4; median sFASI: 145,8pg/ml p=0,019; and median sFASI: 64,95pg/ml p=0,007 respectively). IL-10 levels also appeared to be higher in definitive ALPS patients. IL-18 showed no difference.

Conclusions In conclusion, annexin levels are a useful marker for ALPS patients but only with FAS mutations. While DNT rate, IL-10 levels can confirm these results, our data show that IL-18 is a poor marker for ALPS.