Profile of Autoantibodies Against Phosphorylcholine and Cross-reactivity to Oxidation-Specific Neoantigens in Selective IgA Deficiency With or Without Autoimmune Diseases

Abstract

Immunoglobulin A deficiency (IgAD) is considered the most common form of primary immunodeficiency. The majority of IgA-deficient individuals are considered asymptomatic, even though IgAD has been associated with an increased frequency of recurrent infections, allergy, and autoimmune diseases. In this study we evaluate the Natural autoantibodies (NatAbs) reactivity to phosphorylcholine (PC) and to some pro-inflammatory molecules in IgAD with or without autoimmune disorders. We observed that in the absence of IgA there is an enhancement of IgG subclasses functioning as NatAbs against PC. Immunoglobulin G (IgG) against lipopolysaccharide, C-reactive protein, and IgA was found in IgAD, regardless of the autoimmune manifestations. Nonetheless, IgAD patients with autoimmune disease showed significantly higher IgG reactivity against pro-inflammatory molecules, such as cardiolipin, oxidized low-density lipoproteins, and phosphatidylserine, with positive correlation between them. In conclusion, the IgG NatAbs against PC may represent a compensatory defense mechanism against infections and control excess of inflammation, explaining the asymptomatic status in the IgA deficiency.

Microbial Modulation of Host Immunity with the Small Molecule Phosphorylcholine

“…While the majority of ChoP-specific antibodies are IgM natural antibodies (122), human ChoP-specific IgG is protective against H. influenzae and S. pneumoniae in mouse models of infection (102). Patients with specific antibody defects, such as IgA-deficient patients, also have elevated levels of anti-ChoP IgG (123). Several vaccine formulations have demonstrated promise for the induction of ChoP-specific responses in animal models of infection with S. pneumoniae (124), N. meningitidis (125), and H. influenzae (126).…”

Autoimmune diseases and autoantibodies in pediatric patients and their first-degree relatives with immunoglobulin A deficiency

“…Both systemic and organ-specific autoimmune diseases have been described in association with IgAD 13 and the main autoimmune disorders associated with this immunodeficiency were: hypothyroidism, CD and rheumatic diseases. [9][10][11][12][13]26 Recently, IgAD has also been evidenced in 4% of our c-SLE population. 27 Additionally, hematologic autoimmune disorders are very frequent in PID patients, especially antibody deficiencies, such as common variable immunodeficiency and IgAD, particularly idiopathic thrombocytopenic purpura and autoimmune haemolytic anemia, as evidenced in two of our IgAD patients.…”

“…10 Of note, autoimmune diseases occur in 7-36% of IgAD patients and autoantibodies are observed in more than 40% of the patients. 10,11 The prevalence of IgAD is 1-4% in systemic lupus erythematosus (SLE) patients, 10 2-4% in rheumatoid arthritis (RA) 10 and 2.6% in celiac disease (CD). 12 Furthermore, autoimmune diseases are frequently reported in relatives of IgAD patients.…”

“…Among the first-degree relatives of IgAD patients, 10% had autoimmune diseases compared to 5% in general population. [11][12][13][14][15] However, to our knowledge, the concomitant evaluation of autoimmune diseases and auto antibodies in a cohort of IgAD patients with current age greater than 10 years and their relatives with IgAD has not been studied.…”

Compensatory IgM to the Rescue: Patients with Selective IgA Deficiency Have Increased Natural IgM Antibodies to MAA–LDL and No Changes in Oral Microbiota

“…Also, compensatory elevation in IgG levels in SIgAD patients has been observed (17--19). An enhancement in IgG reactivity to phosphorylcholine was reported in a study comparing SIgAD patients and healthy controls (20).…”