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.