Should my patient with COPD and recurrent exacerbations undergo evaluation for antibody deficiency?

Although there are no consensus guidelines on when to evaluate patients with COPD for antibody deficiency, we should at least consider this possibility in patients with recurrent exacerbations despite maximal inhaled therapy (long-acting beta-2 agonist-LABA, long-acting muscarinic antagonist-LAMA and inhaled corticosteroids).1

Couple of retrospective studies of common variable immunodeficiency (CVID) in patients with COPD have reported a prevalence ranging from 2.4% to 4.5%. 1 In another study involving 42 patients thought to have had 2 or more moderate to severe COPD exacerbations per year—often despite maximal inhaled therapy— 29 were diagnosed  with antibody deficiency syndrome, including 20 with specific antibody deficiency (SAD), 8 with CVID and 1 with selective IgA deficiency.2  Although systemic corticosteroids may lower IgG and IgA levels, the majority of the patients in this study were not taking any corticosteroids at the time of their evaluation.

In another study involving patients undergoing lung transplantation, pre-transplant mild hypogammaglobulinemia was more prevalent among those with COPD (15%) compared to other lung conditions (eg, cystic fibrosis), independent of corticosteroid use.3  A favorable impact of immunoglobulin therapy or chronic suppressive antibiotics on reducing recurrent episodes of COPD exacerbation in patients with antibody deficiency has also been reported, supporting the clinical relevance of hypogammaglobulinemia in these patients. 2,4 

Remember that even normal quantitative serum immunoglobulin levels (IgG, IgA, and IgM) do not necessarily rule out antibody deficiency. Measurement of IgG subclasses, as well as more specific antibodies, such as those against pneumococcal polysaccharides may be required for further evaluation.

See a related pearl at https://pearls4peers.com/2015/07/12/my-65-year-old-patient-has-had-several-bouts-of-bacterial-pneumonia-in-the-past-2-years-her-total-serum-immunoglobulins-are-within-normal-range-could-she-still-be-immunodeficient/.

Contributed in part by Sydney Montesi, MD, Mass General Hospital, Boston, MA.

References

  1. Berger M, Geng B, Cameron DW, et al. Primary immune deficiency diseases as unrecognized causes of chronic respiratory disease. Resp Med 2017;132:181-188. https://www.sciencedirect.com/science/article/pii/S0954611117303554
  2. McCullagh BN, Comelias AP, Ballas ZK, et al. Antibody deficiency in patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD). PLoS ONE 2017; 12: e0172437. https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0172437
  3. Yip NH, Lederer DJ, Kawut SM, et al. Immunoglobulin G levels before and after lung transplantation 2006;173:917-21.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662910/
  4. Cowan J, Gaudet L, Mulpuru S, et al. A retrospective longitudinal within-subject risk interval analysis of immunoglobulin treatment for recurrent acute exacerbation of chronic obstructive pulmonary disease. PLoS ONE 2015;10:e0142205. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142205

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Should my patient with COPD and recurrent exacerbations undergo evaluation for antibody deficiency?

My patient with erythema multiforme has tested positive for Mycoplasma pneumoniae IgM antibody. Does this mean she has an acute M. pneumonia infection as the cause of her acute illness?

Not necessarily! Although detection of IgM in the serum of patients has proven valuable in diagnosing many infections during their early phase, particularly before IgG is detected, less well known is that false-positive IgM results are not uncommon. 1

More specific to M. pneumoniae IgM, false-positive results have been reported in 10-80% of patients without a clinical diagnosis of acute M. pneumoniae infection 2-4 and 3-15% of blood donors. 4

False-positive IgM results may also occur when testing for other infectious agents, such as the agent of Lyme disease (Borrelia burgdorferi), arboviruses (eg, Zika virus), and herpes simplex, Epstein-Barr, cytomegalovirus, hepatitis A and measles viruses. 1,5  

Reports of false positive IgM results include a patient with congestive heart failure and mildly elevated liver enzymes who had a false-positive hepatitis IgM which led to unnecessary public health investigation and exclusion from an adult day care center. 1 Another patient with sulfa rash had a false-positive measles IgM antibody resulting in callback of >100 patients and healthcare providers for testing!5

There are many potential mechanisms for false-positive IgM results, including polyclonal B cell activation, “vigorous immune response”, cross-reactive antibodies, autoimmune disease, subclinical reactivation of latent viruses, influenza vaccination, overreading weakly reactive results, and persistence of antibodies long after the resolution of the acute disease. 1,2

In our patient, a significant rise in M. pneumoniae IgG between acute and convalescent samples several weeks apart may be more helpful in diagnosing an acute infection accounting for her erythema multiforme.

 

References

  1. Landry ML. Immunoglobulin M for acute infection: true or false? Clin Vac Immunol 2016;23:540-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933779/
  2. Csango PA, Pedersen JE, Hess RD. Comparison of four Mycoplasma pneumoniae IgM-, IgG- and IgA-specific enzyme immunoassays in blood donors and patients. Clin Micro Infect 2004;10:1089-1104. https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)63853-2/pdf
  3. Thacker WL, Talkington DF. Analysis of complement fixation and commercial enzyme immunoassays for detection of antibodies to Mycoplasma pneumoniae in human serum. Clin Diag Lab Immunol 2000;7:778-80. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC95955/
  4. Ryuta U, Juri O, Inoue Y, et al. Rapid detection of Mycoplasma pneumoniae IgM antibodies using immunoCard Mycoplasma kit compared with complement fixation (CF) tests and clinical application. European Respiratory Journal 2012; 40: P 2466 (Abstract). https://erj.ersjournals.com/content/40/Suppl_56/P2466 
  5. Woods CR. False-positive results for immunoglobulin M serologic results: explanations and examples. J Ped Infect Dis Soc 2013;2:87-90. https://www.ncbi.nlm.nih.gov/pubmed/26619450

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My patient with erythema multiforme has tested positive for Mycoplasma pneumoniae IgM antibody. Does this mean she has an acute M. pneumonia infection as the cause of her acute illness?