ROC curve analysis and cut-off values
ROC curve analyses verified that CG and gamma globulin were independent discriminative values to detect IgG levels lower than 600 mg/dL, 500 mg/dL, 400 mg/dL and 300 mg/dL. For CG, AUC (95% CI) values were 0.84 (0.80-0.87) to detect IgG<600mg/dL (p<0.001), 0.84 (0.80-0.87) to detect IgG<500 mg/dL (p<0.001), 0.82 (0.78-0.86) to detect IgG<400 mg/dL and 0.82 (0.77-0.88) to detect IgG<300 mg/dL (p<0.001). For gamma globulin, AUC (95% CI) values were 0.94 (0.92-0.96) to detect IgG<600mg/dL (p<0.001), 0.95 (0.92-0.97) to detect IgG<500mg/dL (p<0.001), 0.95 (0.92-0.98) to detect IgG<400mg/dL (p<0.001) and 0.96 (0.94-0.99) to detect IgG<300mg/dL (p<0.001) (Figure 3).
Sensitivity and specificity of each CG and gamma globulin values against each of the IgG levels were calculated through the analysis of the ROC curves as shown in Table 2. Since we considered IgG <600 mg/dl as the limit for hypogammaglobulinemia, the CG value predicting patients with IgG <600 mg/dl as a screening test was determined as <2.0 with 83.8% sensitivity and 74.9% specificity. The gamma globulin value which predicted the same IgG value of the patients with 89.0% sensitivity and 89.4% specificity was determined as <0.7.
When the patients with a CG cut-off value of <2.0 were evaluated according to the features of suggestive immunodeficiency such as the presence of infections and recurrent parenteral antibiotic usage, univariate analysis showed that the frequency of pneumonia, presence of infections with opportunistic microorganisms and the frequency of parenteral antibiotic usage were higher in these patients with CG less than 2 g/dL than the ones with CG higher than 2 g/dL (p=0.003, p=0.003 and p<0.001, respectively) (Table 3A). Multivariate analysis of the model designed according to univariate analysis showed that the frequency of parenteral antibiotic usage was higher in patients with a CG cut-off value of <2.0 than the others (p=0.025) (Table 3B).
When the patients whose IgA and IgM values lower than the reference values (70-400 mg/dL, 40-230 mg/dL, respectively) were compared, the number of patients with CG <2.0 was significantly higher than those with CG ≥2.0 (p<0.001, p<0.001, respectively) and similarly, the number of patients with gamma globulin <0.7 was significantly higher than those with gamma globulin ≥0.7 (p<0.001, p<0.001, respectively). In patients with CG <2.0, 78.1% of them had an IgA value of <70 mg/dL and 64.8% of them had an IgM value of <40 mg/dL; and in patients with gamma globulin <0.7, 87.1% of them had an IgA value of <70 mg/dL and 79.2% of them had an IgM value of <40 mg/dl.