Camurati-Engelmann disease (CED) is a progressive, autosomal dominant sclerosing bone dysplasia involving gene mutation of the latency-associated peptide of tumor growth factor (TGF)-β1, preventing inactivation of the cytokine. Since TGF-β is thought to play a regulatory role in immunity, one might expect an immune dysfunction in CED.

By retrospective chart review, a mother and daughter with CED were identified.

The mother had a history of asthma, chronic gastrointestinal complaints, tobacco use, recurrent conjunctivitis, urinary tract infections, vaginal yeast infections, and monthly bronchitis. She had normal IgG and IgA, low IgG2, normal IgG4, low IgM of 48 (normal 60-263 mg/dl), and high IgE of 1709 (normal 2-120 IU/ml). However, she had inadequate anti-polysaccharide antibody response, anergy by DTH skin testing, and no response to recall antigens in vitro. She had normal serum TGF-β, but elevated serum IFN-γ, IL-4, and TNF-⍺. The daughter had documented CED gene mutation, bone pain, fatigue, loss of appetite, recurrent bronchitis and pharyngitis, requiring multiple courses of antibiotics. She had normal IgG and IgA, normal IgG subclasses, low IgM of 55, increased IgE of 192, normal anti-polysaccharide antibody response, and normal in vitro lymphocyte testing, but anergic DTH skin testing. Unlike her mother, she had non-detectable serum cytokine levels.

These patients reflect that gene mutation of the TGF-β1 latency-associated peptide is associated with immune dysfunction. Individual differences in immune abnormalities may parallel the variable, and progressive, bone manifestations seen in these patients. We anticipate the daughter's immune dysfunction to become more overt with age.