Frequency and Manifestations of Autoimmunity Among Children Registered in the Kuwait National Primary Immunodeficiency Registry

Abstract

Objectives: To present a prospective report on the characteristics of autoimmune manifestations in patients with primary immunodeficient children registered in the Kuwait National PIDs Registry (KNPIDR).Methods: The data were obtained from the Kuwait National Primary Immunodeficiency Disorders Registry during the period of January 2004 to December 2019.Results: A total of 286 PID children were registered in KNPIDR during the study period with a predominance of immunodeficiencies affecting cellular and humoral immunity followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Fifty-seven (19.9%) patients presented with a total of 107 autoimmune manifestations. There was no significant statistical association between autoimmune manifestations and gender. Patients with autoimmune manifestations were older at onset of PID symptoms compared to those with no such manifestations, but this did not reach level of significance. The diagnosis delay was longer in patients with autoimmune manifestations compared to those with no such manifestations (p = 0.038). Forty-seven percent of these manifestations were among the presenting symptoms while 53% were documented later during the course of the disease. Fifty-seven percent of the patients developed 1 autoimmune manifestation, 30% developed 2 such manifestations, and 16% had ≥3 autoimmune manifestations. The most common autoimmune manifestation was cytopenia, followed by gastrointestinal manifestations and manifestations of the skin, hair, and nails. Autoimmune cytopenia were more common in patients with immune dysregulation syndromes, while gastrointestinal and skin manifestations predominate in patients with immunodeficiencies affecting cellular and humoral immunity and endocrine manifestations were more common in immune dysregulation syndromes. There were significant statistical associations between developing autoimmune manifestations and death as well as PID categories, being more common in patients with immune dysregulation. The frequency of autoimmunity was high among patients with RAG, WAS, STAT5b, NF-κB2, Fas, FasL, LRBA, APECED, IL-10, and C4 deficiencies.Massaad et al. Autoimmunity in Primary ImmunodeficienciesConclusions: Autoimmunity is frequent in patients with PIDs in Kuwait. This should prompt the suspicion of a PID in patients who present initially with autoimmunity, especially autoimmune cytopenia. Such patients should be managed with extra care since they are at a higher risk of death.

Diagnostic and Predictive Contribution of Autoantibodies Screening in a Large Series of Patients With Primary Immunodeficiencies

“…Furthermore, gastrointestinal disorders (10.0%), rheumatologic diseases (3.7%) and endocrine disorders (3.3%) were also common in our series. This is comparable to the percentages found in the French study (9.5%, 5.0% and 3.2%, respectively) ( 6 , 8 ). However, skin manifestations, which have been observed in 3.3% of our patients were more frequent in the French registry (5.5%) ( 6 ).…”

“…A similar prevalence (26.2%) has been reported in a previous study of the French National Primary Immunodeficiencies Registry ( 6 ). However, the frequency of AIDs in the Slovenian (22%) and Kuwaiti (20%) studies were lower ( 8 , 10 ). Many factors, such as ethnicity, environment, cohort size, age of patients, disease duration, and access to hematopoietic stem cell transplantation could have contributed to such differences between series.…”

“…Autoimmunity has been widely studied in PIDs. However, most of published studies were focused on clinical manifestations and only few is known about the clinical relevance of autoantibody testing in such monogenic defects ( 6 , 8 ). In the present study, a large series of patients with PIDs have been screened for a broad panel of autoantibodies.…”

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity

“…Among patients with autoimmunity, hematologic (42.2%), rheumatologic (26.7%), gastrointestinal (27.2%), dermatologic (16.7%), neurologic (7.8%), and endocrine (7.8%) affected organs by autoimmune diseases were documented. Moreover, in patients with monogenic IEIs, immune thrombocytopenic purpura (ITP) (6.5%), juvenile idiopathic arthritis (JIA) (4.8%), and autoimmune TA B L E 1 Demographic data in patients with monogenic inborn errors of immunity 11 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) 13 (8-21.5) 11 (5.7-20) .030 * 11 (6.5-21.5) 14.5 (10.2-21.5) .307…”

“…. The prevalence of polyautoimmunity and the number of autoimmunities per individual in patients with IEIs are not clear; however, several recent studies [18][19][20] have partly addressed these uncertainties. In the present study, among 92 patients with autoimmune disorders, 64 (69.6%) patients had a single type of autoimmunity, 19 (20.6%) patients had two, 4 (4.3%) patients had three, and 5 (5.4%) patients had four types of autoimmunities.…”