PID Resources

X-linked Hyper-IgM Syndrome (HIGM)

Definitive

Male patient with serum IgG concentration at least 2 SD below normal for age and one of the following:

  1. Mutation in the CD40L gene
  2. Maternal cousins, uncles, or nephews with confirmed diagnosis of XHIM 

Probable

Male patient with serum IgG concentration at least 2 SD below the normal for age and all of the following:

  1. Normal number of T cells and normal T cell proliferation to mitogens
  2. Normal or elevated numbers of B cells but no antigen specific IgG antibody
  3. One or more of the following infections or complications
-Recurrent bacterial infections in the first 5 years of life
-Pneumocystis carinii infection in the first year of life
-Neutropenia
-Cryptosporidium-related diarrhea
-Sclerosing cholangitis
-Parvovirus induced aplastic anemia
  1. Absent CD40 ligand cell surface staining on activated CD4+T cells as assessed by binding to soluble CD40 or monoclonal antibody to CD40 ligand

Possible

Male patient with serum IgG concentration at least 2 SD below normal for age, normal numbers of T cells and B cells and one or more of the following:

  1. Serum IgM concentration at least 2 SD above normal for age
  2. Pneumocystis carinii infection in the first year of life
  3. Parvovirus induced aplastic anemia
  4. Cryptosporidium-related diarrhea
  5. Severe liver disease (sclerosing cholangitis)
 

Spectrum of disease

Patients with XHIM have recurrent bacterial and opportunistic infections starting in the first year of life. Pneumocystis carinii pneumonia is a common presenting infection. Other patients may have chronic, profuse diarrhea requiring parenteral nutrition. Over 50% of patients have chronic or intermittent neutropenia, often associated with oral ulcers. Cryptosporidium infection may lead to severe bile duct disease and hepatic cancer. Serum concentration of IgG is usually less than 200 mg/dl; IgM may be low, normal or elevated. Atypical cases may present with recurrent infections, anemia or hepatitis in the second or third decade of life.

XHIM exclusion criteria

  1. Defects in T cell activation (i.e., defective expression of CD69 or CD25 after in vitro T cell activation)
  2. Human immunodeficiency virus infection
  3. Congenital rubella infection
  4. MHC class II deficiency
  5. CD4+T cell deficiency
  6. Drug or infection exposure known to influence the immune system
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