As protein-losing enteropathy (PLE) can lead to hypogammaglobulinemia and lymphopenia, and since common variable immunodeficiency (CVID) is associated with digestive complications, we wondered if: 1/PLE could occur during the course of CVID; and 2/PLE was associated with specific immunological anomalies that differed from CVID.
Patients were classified in 3 groups: CVID+PLE+ (n=5), CVID+PLE- (n=21), PLE+CVID- (n=12). PLE was diagnosed using α1-antitrypsin faecal clearance or Gordon-Waldmann test. Immunoglobulin (Ig) A, G and M levels, and naïve/memory B and T cell subsets were compared between each group.
Most CVID+PLE+ patients had multiple causes of PLE: inflammatory bowel disease (3/5), nodular regenerative hyperplasia (2/5), villous atrophy (1/5), giardiasis (2/5). Compared to the CVID+PLE- group, CIVD+PLE+ patients had lower IgM levels (0.04±0.0045 vs 0.53±1.5g/l, p<0.001) and IgG substitution efficiency index (36±6.2 vs 81±26, p=0.002); but similar IgA and pre-substitution IgG levels, B and T cells counts and subset distribution. Compared to the CVID+ PLE- group, PLE+ CVID- patients did not develop infectious complications; had higher serum IgA (1.24±0.66g/l vs 0.13±0.12, p<0.001), IgG (3.8±1.7g/l vs 1.9±1.4, p=0.007) and switched memory B cells (8.5±6.2 vs 2.8±5.6%, p=0.001) levels; lower naïve CD4 (12±9.3 vs 33±22%, p=0.004) and naïve CD8 (7.3±9.9 vs 38±20%, p<0.001) T cells levels; and similar IgM, naïve and marginal zone B cells levels.
PLE can occur during CVID and requires higher Ig replacement therapy dosing. PLE can also mimic CVID and is associated with milder immunological abnormalities, notably mildly decreased to normal serum IgA levels.