ALLERGIC AND IMMUNOLOGIC CONDITIONS

Selective IgA Deficiency

Classification: Primary humoral immunodeficiency with isolated severe reduction of IgA (Kishiyama et al., 2019).

Key diagnostic discriminator: Markedly depressed serum IgA with normal IgG and IgM. Many patients are asymptomatic; recurrent mucosal infection, allergy, autoimmunity, or a transfusion reaction may reveal the disorder (Kishiyama et al., 2019).

Clinical priority: Anaphylaxis during a transfusion requires immediate emergency management and later immunology/transfusion evaluation (Kishiyama et al., 2019).

Etiology and risk factors

  • The defect is heterogeneous and often reflects impaired maturation of IgA-producing B cells. Familial clustering and overlap/evolution with CVID can occur (Kishiyama et al., 2019).
  • It is the most common primary immunodeficiency in many populations. Most affected people remain clinically well (Kishiyama et al., 2019).

Pathophysiology

  • Secretory IgA normally limits adherence and invasion at respiratory, gastrointestinal, and genitourinary mucosa. Deficiency weakens this barrier, although compensatory secretory IgM may limit disease (Kishiyama et al., 2019).
  • Some patients form anti-IgA antibodies after exposure and are at risk for a severe transfusion reaction, but this is uncommon and not universal (Kishiyama et al., 2019).

Clinical manifestations

  • Often no symptoms. Possible recurrent sinusitis, otitis, pneumonia, Giardia or chronic diarrhea, atopy, food allergy, asthma, or autoimmune disease (Kishiyama et al., 2019).
  • A history of immediate reaction to plasma-containing blood products is an important clue in a patient with severe IgA deficiency (Kishiyama et al., 2019).

Findings that argue against or redirect

  • Low IgA in a child younger than 4 years may reflect delayed maturation and should not be prematurely labeled as permanent selective deficiency (Kishiyama et al., 2019).
  • Low IgG and poor broad vaccine responses suggest CVID or another combined defect. Protein loss, medication, infection, or other secondary cause must be considered (Kishiyama et al., 2019).
  • Normal IgA on repeat testing argues against the diagnosis (Kishiyama et al., 2019).

Diagnostic evaluation

  • Measure quantitative IgA, IgG, and IgM. If infection is clinically important, assess antibody function and lymphocyte populations and exclude a broader or secondary immune disorder (Kishiyama et al., 2019).
  • Interpret the finding in the context of age, symptoms, associated allergic or autoimmune disease, and possible evolution toward a broader antibody deficiency (Kishiyama et al., 2019).

Expected diagnostic and laboratory findings

  • The characteristic laboratory pattern is a marked isolated reduction of serum IgA with normal IgG and IgM (Kishiyama et al., 2019).
  • A subset of patients develops anti-IgA antibodies and may experience a severe reaction to plasma-containing blood products (Kishiyama et al., 2019).

Differential diagnosis

  • CVID: low IgG plus low IgA/IgM and impaired vaccine responses (Kishiyama et al., 2019).
  • Transient low IgA in childhood: age and recovery on repeat testing distinguish it (Kishiyama et al., 2019).
  • Secondary hypogammaglobulinemia/protein loss: affects additional immunoglobulins or has a causal systemic disorder (Kishiyama et al., 2019).
  • Chronic mucosal disease with normal IgA: consider anatomic, ciliary, allergic, infectious, or other immune causes (Kishiyama et al., 2019).

Treatment and management

  • No specific treatment is required for most patients. Treat recurrent infection and associated allergic or autoimmune disease according to the clinical problem (Kishiyama et al., 2019; Norris, 2020).
  • Document any previous transfusion reaction and coordinate future blood-product selection with transfusion medicine (Kishiyama et al., 2019; Norris, 2020).

Additional complications and red flags

  • Monitor clinically because a minority of patients develop broader antibody deficiency over time (Kishiyama et al., 2019).

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References

Kishiyama, J. L., Chang, J. J., & Donovan, S. M. (2019). Disorders of the immune system. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed.). McGraw-Hill Education.

Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer.