Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions

Abstract

The common variable immunodeficiency disorders are a mixed group of heterogeneous conditions linked by lack of immunoglobulin production and primary antibody failure. This variability results in difficulty in making coherent sense of either immunopathogenesis or the role of various genetic abnormalities reported in the literature. The recent attempt to collate the varied complications in these conditions and to define particular clinical phenotypes has improved our understanding of these diseases. Once refined and confirmed by other studies, these definitions will facilitate improved accuracy of prognosis and better management of clinical complication. They may also provide a method of analysing outcomes as related to new immunopathological and genetic findings.

Figure 1

Figure 1(a): European Cohort: Serum Immunoglobulin isotypes at diagnosis. Patients are divided into four boxes depending on their presenting IgA level. Each box is subdivided by the IgM level into three columns, with those with the lowest IgM levels (≤0.1 g/l) in the first column; those with the highest IgM (>0.5 g/l) in the third column and those with IgM levels between (0.11-0.5 g/l) in the second column. Each column is divided into three, depending on the IgG level; those in the lower part with IgG ≤ 1.0 g/l; those with IgG > 3.0≤ 6.5 g/l at the top and those with IgG 1.1-3 g/l in the middle. The number of patients in each group is in each box and plotted on the y-axis. (from Chapel et al 2008 with permission from Blood) Figure 1(b): United States Cohort: Serum Immunoglobulin isotypes at diagnosis. Similar to Figure 1a, 349 subjects from one medical centre (Mount Sinai, NYC) are divided into the same categories based on presenting serum immunoglobulin levels.

Figure 1

Figure 1(a): European Cohort: Serum Immunoglobulin isotypes at diagnosis. Patients are divided into four boxes depending on their presenting IgA level. Each box is subdivided by the IgM level into three columns, with those with the lowest IgM levels (≤0.1 g/l) in the first column; those with the highest IgM (>0.5 g/l) in the third column and those with IgM levels between (0.11-0.5 g/l) in the second column. Each column is divided into three, depending on the IgG level; those in the lower part with IgG ≤ 1.0 g/l; those with IgG > 3.0≤ 6.5 g/l at the top and those with IgG 1.1-3 g/l in the middle. The number of patients in each group is in each box and plotted on the y-axis. (from Chapel et al 2008 with permission from Blood) Figure 1(b): United States Cohort: Serum Immunoglobulin isotypes at diagnosis. Similar to Figure 1a, 349 subjects from one medical centre (Mount Sinai, NYC) are divided into the same categories based on presenting serum immunoglobulin levels.

Figure 2. Types of complications in patients with CVIDs and proportions of patients affected

Patients may have had more than one complication (Data from Chapel et al 2008) [Abbreviations: L/N lymphadenopathy;LIP lymphoid interstitial pneumonitis; NHR nodular regenerative hyperplasia].

Figure 4. Survival of patients with CVIDs, by years since diagnosis and by clinical phenotype

(a) Yellow line represents those patients without complications. (b) Turquoise line represents those patients with at least one disease related complication. Kaplan-Meier plot of survival. (Data from Chapel et al 2008)