Welcome to the “Clinical Pearl of the Month” series in which a clinical tidbit or key fact related to primary immunodeficiency diseases will be posted to the NIT/FIT listserv on a regular basis. These pearls are provided by your fellow volunteer NIT/FIT members, and we hope that you will find these small nuggets of information useful in practice, teaching, or exam study.
- Diagnosing complement deficiency in young children is challenging, especially since age-matched reference ranges are not always available for complement tests. Remember to check CH50, AH50, and mannose binding lectin first to evaluate all 3 arms of complement, then check individual components as needed. While values close to zero likely represent true deficiency, reduced but not absent values likely represent partial function with variable clinical phenotype. Checking complement split products and/or complement regulatory proteins may be warranted in select cases. Genetic testing of individual components is rarely necessary.
- Although infections with encapsulated bacteria (e.g., Neisseria) are the best-remembered consequence of complement deficiency, it is important to consider and evaluate these patients for autoimmunity (including systemic lupus erythematosus-like syndromes).
- Complement deficiencies described to date are transmitted as autosomal recessive, except for properdin deficiency which is X-linked.
- In addition to vigilance and prompt initiation of antimicrobials when infections are suspected, routine vaccinations according to CDC guidelines, including live viral vaccines, are considered safe and effective for complement deficient patients. When immunizing these patients, conjugate vaccines may be preferable over pure polysaccharide vaccines. Consider administering conjugate meningococcal vaccine in patients with terminal complement deficiency earlier than CDC recommendations.
- Pettigrew HD, Teuber SS, Gershwin ME. Clinical significance of complement deficiencies. Ann N Y Acad Sci. 2009 Sep;1173:108-23.
- Platonov AE, Vershinina IV, Kuijper EJ, et al. Long term effects of vaccination of patients deficient in a late complement component with a tetravalent meningococcal polysaccharide vaccine. Vaccine 2003; 21:4437.<
- Jönsson G, Lood C, Gullstrand B, et al. Vaccination against encapsulated bacteria in hereditary C2 deficiency results in antibody response and opsonization due to antibody-dependent complement activation. Clin Immunol 2012; 144:214.
- Briere EC, Rubin L, Moro PL, et al. Prevention and control of haemophilus influenzae type b disease: recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep 2014; 63:1.
The constellation of hypogammaglobulinemia, mucocutaneous candidiasis and eosinopenia/basopenia should prompt evaluation for thymoma (Good’s syndrome), which can be associated with anti-cytokine (anti-IL-17A/F) auto-antibodies.
- Acquired basophil and eosinophil deficiency in a patient with hypogammaglobulinaemia associated with thymoma. Mitchell EB, Platts-Mills TA, Pereira RS, Malkovska V, Webster AD. Clin Lab Haematol. 1983;5(3):253-7.
- Mucocutaneous candidiasis and autoimmunity against cytokines in APECED and thymoma patients: clinical and pathogenetic implications. Kisand K, Lilic D, Casanova JL, Peterson P, Meager A, Willcox N. Eur J Immunol. 2011 Jun;41(6):1517-27.