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

Mella, Miia A.; Lavrinienko, Anton; Akhi, Ramin; Hindström, Rasmus; Nissinen, A; Wang, Chunguang; Kullaa, Arja; Salo, Tuula; Auvinen, Juha; Koskimäki, Janne J.; Hörkkö, Sohvi

doi:10.4049/immunohorizons.2100014

Cited by 5 publications

(2 citation statements)

References 71 publications

(92 reference statements)

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“…IgAD is a heterogenous disease with maltitude pathogenic approaches; the major underlying cause of IgAD centers around B-cell proliferation, maturation, and ultimately immunoglobulin production [ 34 ]. Lack of IgA production tend to incite compensatory increase in secretory IgM [ 35 ]. Many studies have pointed out an increased risk of atopic diseases in IgAD including bronchial asthma, allergic rhinitis, and atopic dermatitis [ 25 , 31 , 36 – 39 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical manifestation for immunoglobulin A deficiency: a systematic review and meta-analysis

Vosughimotlagh,

Rasouli,

Rafiemanesh

et al. 2023

Allergy Asthma Clin Immunol

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Objectives Immunoglobulin A deficiency (IgAD) is a common disease with an unknown genetic defect, characterized by the decreased or absent IgA with other isotypes normal, normal subclasses, and specific antibodies. Patients with this disorder represent a spectrum of clinical manifestations including infections, autoimmune disorders, malignancy, and allergic diseases. The current study aimed to evaluate their prevalence and categorized them. Methods We searched PubMed, Web of Science, and Scopus databases to find eligible studies from the earliest available date to January 2022 with standard keywords. Pooled estimates of clinical manifestations prevalence and the corresponding 95% confidence intervals were calculated using random-effects models. Results The most prevalent clinical manifestations belonged to infection (64.8%) followed by allergic diseases (26.16%) and autoimmunity (22.0%), respectively. In selective IgA deficiency patients as the largest group of IgAD in current study, celiac disease (6.57%), Inflammatory bowel disease (4.01%), and rheumatoid arthritis (3.80%) were the most prevalent autoimmunity. Meanwhile, the most frequent infection was respiratory tract infection, fungal infection, and gastrointestinal infection at 50.74%, 18.48%, and 15.79%, respectively. In addition, the pooled prevalence of asthma, allergic rhinitis, and allergic conjunctivitis were 19.06%, 15.46%, and 11.68%, respectively which were reported as the most widespread allergic diseases. Conclusions Our results showed that apart from undiagnosed IgAD patients, IgAD patients represent a wide range of clinical manifestations. Infection, allergy, and autoimmunity are the most common clinical manifestations. The concurrent presence of IgA and IgG subtypes deficiency could be associated with increased susceptibility to infection. Considering the probability of developing new clinical complications during follow-up, periodic assessments of IgAD patients should be inspected.

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Section: Discussionmentioning

confidence: 99%

Clinical manifestation for immunoglobulin A deficiency: a systematic review and meta-analysis

Vosughimotlagh,

Rasouli,

Rafiemanesh

et al. 2023

Allergy Asthma Clin Immunol

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“…Asymptomatic patients account for more than half of SIgAD cases, and depending on the estimates, up to 89% of cases [111,148]; these healthy patients who were tested for a different reason in whom IgA deficiency was a collateral finding do not require follow-up. The asymptomatic phenotype is probably due to compensatory mechanisms for the lack of IgA (among which are postulated an increased production of IgM [149], IgG, and increased APRIL, which is involved in B cell development and survival [150]. However, not all studies concur on the finding of increased secretory IgM production in asymptomatic SIgAD patients compared to those that are infectious-prone [151].…”

Section: Clinical Phenotypesmentioning

confidence: 99%

Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

Sircana,

Vidili,

Gidaro

et al. 2023

IJTM

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Inborn errors of immunity (IEI) are multifaced diseases which can present with a variety of phenotypes, ranging from infections to autoimmunity, lymphoproliferation, and neoplasms. In recent decades, research has investigated the relationship between autoimmunity and IEI. Autoimmunity is more prevalent in primary humoral immunodeficiencies than in most other IEI and it can even be their first manifestation. Among these, the two most common primary immunodeficiencies are selective IgA deficiency and common variable immunodeficiency. More than half of the patients with these conditions develop non-infectious complications due to immune dysregulation: autoimmune, autoinflammatory, allergic disorders, and malignancies. Around 30% of these patients present with autoimmune phenomena, such as cytopenia, gastrointestinal and respiratory complications, and endocrine and dermatologic features. Complex alterations of the central and peripheral mechanisms of tolerance are involved, affecting mainly B lymphocytes but also T cells and cytokines. Not only the immunophenotype but also advances in genetics allow us to diagnose monogenic variants of these diseases and to investigate the pathogenetic basis of the immune dysregulation. The diagnosis and therapy of the primary humoral immunodeficiencies has been mostly focused on the infectious complications, while patients with predominant features of immune dysregulation and autoimmunity still present a challenge for the clinician and an opportunity for pathogenetic and therapeutic research.

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Levels of Natural Antibodies Before and After Immunoglobulin Replacement Treatment Affect the Clinical Phenotype in Common Variable Immunodeficiency

Sarrigeorgiou,

Tsinti,

Kalala

et al. 2024

J Clin Immunol

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Natural antibodies (NAbs) occurring in individuals without prior exposure to specific antigens, provide direct first barrier protection against pathogens, and exert immunoregulation thus actively contributing to the maintenance of immune homeostasis, controlling inflammatory processes and preventing autoimmunity. Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by a compromised immune function that brings into focus the role of NAbs. Our aim was to explore whether NAb levels could serve as potential key indicators in CVID for monitoring disease progression and predicting outcomes. In this study, we analyzed a Hellenic cohort of 56 patients with CVID (31 newly diagnosed and 25 under immunoglobulin replacement therapy-IgRT) and 33 healthy controls, for total Ig levels and serum IgM and IgG NAb levels against five informative target-antigens of NAbs, namely, actin, DNA, carbonic anhydrase, F(ab΄) 2 fragments of human IgG and TriNitroPhenyl. In addition, follow-up pre- and post- IgRT samples were analyzed in ten (10) patients of our cohort. Results showed that Ig-treated patients exhibited significantly lower IgM NAb levels than untreated patients and healthy controls against all panel antigens. In the follow-up samples, pre-treatment IgM NAb levels negatively correlated with total serum IgM. This imbalance was only partially restored after IgRT, with a significant decrease in IgM NAb levels observed in nine out of ten patients. Moreover, post-treatment patients with recurrent infections presented significantly lower IgM NAb levels, a reduction also observed in patients with bronchiectasis independently of treatment status. On the contrary, post-treatment patients with enteropathy had significantly higher IgM NAb levels against all panel antigens, an increase also noted in patients with autoimmune diseases. Regarding IgG NAbs, replacement therapy restored levels to those of healthy controls. In conclusion, impaired NAb levels are found in CVID patients, particularly related to certain phenotypes. Moreover, the significant decrease in IgM NAb levels after IgRT suggests a potential association with disease course and complications. The results suggest that administration of human IgM NAbs may be an effective combinatorial treatment in selected patients. Further research is needed to understand the functional roles of NAbs in CVID and its complex clinical phenotypes. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-024-01805-7.

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

Cited by 5 publications

References 71 publications

Clinical manifestation for immunoglobulin A deficiency: a systematic review and meta-analysis

Clinical manifestation for immunoglobulin A deficiency: a systematic review and meta-analysis

Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

Levels of Natural Antibodies Before and After Immunoglobulin Replacement Treatment Affect the Clinical Phenotype in Common Variable Immunodeficiency

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