SEARCH

SEARCH BY CITATION

Keywords:

  • allergy;
  • common variable immunodeficiency;
  • hypogammaglobulinemia;
  • immunoglobulin G

Common variable immunodeficiency (CVID) is characterized by pan-hypogammaglobulinemia and recurrent sinopulmonary infection. As both immunoglobulin (Ig)G and the other immunoglobulin isotypes, including IgE, are low (1) and the Th1 cytokines interleukin (IL)-12 and interferon (IFN)-γ are elevated in many patients with CVID (2), it is speculated that IgE-mediated allergic diseases occur rarely in CVID patients. However, Schwartz et al. (3) reported on an adult with co-existing allergic bronchopulmonary aspergillosis and CVID. Here, we present a case of CVID with seasonal allergic symptoms and decreased serum IgG levels during the allergic season.

SJW was a 32-year-old man who had suffered from recurrent pneumonia since the age of 23. He was diagnosed with CVID at another hospital and had received immunoglobulin replacement therapy regularly. He was transferred to our hospital in late-1996. At presentation, T3, T4, T8, B, and natural killer (NK) cells were 83.0, 7.6, 70.5, 6.7, and 6.8%, respectively; IgG, IgA, and IgM levels were 508, <31, and <29 mg/dl, respectively; IgE was <27.4 IU/ml. Human IgG (25 g) had been administered only intermittently, at 2–3-month intervals, for economic reasons. Although the patient rarely needed antibiotics, he complained of sneezing, rhinorrhea, and occasional severe cough at night during spring. Wheezing was heard in his chest at times.

The patient told us that he believed that his serum IgG level was lower in spring. In a review from his chart, his allergic symptoms were recorded almost exclusively from February to May (spring). The average serum IgG level in the years 1997–2003 that was corrected considering the irregular interval of the replacement therapy [median: 69.5 days in spring and 82.0 days from August to November (other seasons)], was significantly lower in spring than in other seasons (228.7 ± 50.6 vs 289.8 ± 73.3 mg/dl, P = 0.018; Fig. 1). The serum total IgE level measured seven times over the past 7 years, including during spring, remained undetectable. Skin prick tests disclosed only weak (+2) responses to alder, willow, pine, and Penicillium extracts.

image

Figure 1. The corrected average serum immunoglobulin G level from February to May was significantly lower than that from August to November in an adult patient with common variable immunodeficiency.

Download figure to PowerPoint

Popa and Nagy (4) reported that allergy skin tests tended to be negative, and total IgE remained <10 IU/ml in CVID. However, one of five patients with CVID was atopic in their report. It has been suggested that the IgE and IgG immune responses are regulated independently. Alternatively, large amounts of serum-specific IgE may not be necessary for a local airway reaction. There is increasing evidence of so-called ‘intrinsic’ asthma related to locally produced IgE.

We demonstrated that the serum IgG level in our CVID patient varied seasonally with his allergic symptoms. Hypogammaglobulinemia in asthmatics is associated with the use of systemic corticosteroids (5), but our patient had never taken systemic steroids. Infants with a family history of atopy are reported to be at increased risk for severe respiratory syncytial virus infection (6). The IL-4- and IL-13-induced inhibition of the Th1 response and consequent suppression of IFN-γ production have been demonstrated in atopy and asthma, which may explain the increased risk for infection. However, this pathway involving IFN-γ is known for cell-mediated immunity. Popa and Nagy (4) showed that, of subjects with IgG deficiency, many were atopic, but they did not mention the possibility of atopy as a contributing factor to IgG deficiency.

To the best of our knowledge, this study is the first to show that atopy exacerbates IgG deficiency in CVID. The exact mechanism remains to be determined.

References

  1. Top of page
  2. References
  • 1
    Waldmann TA, Polmar SH, Balestra ST, Jost MC, Bruce RM, Terry WD. Immunoglobulin E in immunologic deficiency diseases: II. Serum IgE concentration of patients with acquired hypogammaglobulinemia, thymoma and hypogammaglobulinemia, myotonic dystrophy, intestinal lymphangiectasia and Wiskott-Aldrich syndrome. J Immunol 1972;109: 304310.
  • 2
    Webster ADB. Common variable immunodeficiency. Immunol Allergy Clin North Am 2001;21: 122.
  • 3
    Schwartz HJ, Berger M, Hostoffer R. Allergic bronchopulmonary aspergillosis and common variable hypogammaglobulinemia in an adult male patient: case report. J Allergy Clin Immunol 1996;98: 708710.
  • 4
    Popa V, Nagy SM Jr. Immediate hypersensitivity in adults with IgG deficiency and recurrent respiratory infections. Ann Allergy Asthma Immunol 1999;82: 567573.
  • 5
    Hamilos DL, Young RM, Peter JB, Agopian MS, Ikle DN, Barka N. Hypogammaglobulinemia in asthmatic patients. Ann Allergy 1992;68: 472481.
  • 6
    Trefny P, Stricker T, Baerlocher C, Sennhauser FH. Family history of atopy and clinical course of RSV infection in ambulatory and hospitalized infants. Pediatr Pulmonol 2000;30: 302306.