Clinical and Laboratory Features of 184 Italian Pediatric Patients Affected with Selective IgA Deficiency (SIgAD): a Longitudinal Single-Center Study.

PURPOSE: Selective IgA deficiency (SIgAD) is the most common humoral primary immunodeficiency. Long-term follow-up data in large cohort of pediatric patients are scarce. METHODS: We report on a single-center cohort of 184 pediatric patients affected with selective IgA deficiency and describe the characteristics at diagnosis and during follow-up. RESULTS: Respiratory infections were the most common clinical finding leading to the initial diagnosis (62%). Positive family history for antibody deficiencies (selective IgA deficiency, common variable immunodeficiency) led to SIgAD diagnosis in 16% of cases. During follow-up, while the incidence of respiratory infections was not particularly high, gastrointestinal symptoms were reported in 27% of patients. Allergic manifestations were found in 23% at diagnosis and an additional 16% of patients during follow-up, leading to a prevalence of atopy of 39% among SIgAD patients. Autoimmune manifestations, excluding celiac disease, were found in 9% of affected patients during follow-up. Celiac disease was found in a high prevalence (14%). Increase of serum IgA levels to partial deficiency (9%) and normal serum levels for age (4%) was observed during follow-up. A small percentage of patients (2%) progressed to common variable immunodeficiency (CVID). CONCLUSIONS: In conclusion, this is the first study to describe a large single-center pediatric cohort of patients affected with SIgAD, revealing that overall most patients do well with regard to infections. Many develop CD, at a rate much higher than the general population. A few normalize their IgA levels. A few progress to CVID. Thus, careful follow-up is suggested to diagnose and treat potential complications earlier for avoiding potential morbidities.

Adverse events linked with the use of chimeric and humanized anti-CD20 antibodies in children with idiopathic nephrotic syndrome.

AIMS: Anti-CD20 antibodies are increasingly being used to treat idiopathic nephrotic syndrome (INS) in children. While they may allow steroid and calcineurin inhibitor withdrawal, repeated infusions of anti-CD20 antibodies are often required to maintain remission. Data on their potential toxicity in INS are needed, to consider repeated infusions. METHODS: We investigated the side effects associated with the use of rituximab (a chimeric antibody; 130 patients) and ofatumumab (a humanized antibody; 37 patients) in children with INS (steroid-dependent and steroid/calcineurin inhibitor-dependent disease) treated at a national referral centre over a 9-year period (400 treatments; follow-up 1-9 years). RESULTS: Infusion reactions were mainly absent in children with steroid-dependent disease. Rash, dyspnoea, fever, cough and itchy throat (5% and 18% following rituximab and ofatumumab infusion, respectively) were resolved by using premedication with salbutamol. Other short-term reactions (up to 3 months), including arthritis (2%) and lung injury (1%), were more common with rituximab. Infections were observed 3-9 months following infusion, were similarly common in the two groups and resolved with targeted therapies [antibiotic, fluconazole, immunoglobulins (Igs), etc.]. The number of circulating CD19/20 cells fell to 0 at month 1 and were reconstituted at month 3; circulating IgG antibodies remained within the normal range for 1 year. Tetanus and hepatitis B virus immunization was not modified by either treatment; Epstein-Barr virus and John Cunningham virus activation markers were occasionally observed. CONCLUSION: Overall, the toxicity of anti-CD20 monoclonal antibodies was limited to post-infusion side effects in children with more complex disease. The relatively safe profile of anti-CD20 antibodies supports their use as steroid-sparing agents in children with INS.