Background
Methods
Selection of Subjects
General Criteria for Selection of Study Subjects
CVID and IgGSD Index Cases
Control Subjects
Family Members
Laboratory Methods
Statistical Considerations
Results
General Characteristics of CVID and IgGSD Index Patients
Characteristic | CVID (n = 114) | IgGSD (n = 126) |
---|---|---|
Men: Women | 32: 82 | 38: 88 |
Age at Diagnosis, y (range) | 54 ± 16 (21 – 87) | 51 ± 13 (18 – 89) |
Serum Total IgG, mg/dL (range) | 527 ± 115 (140 – 697) | 953 ± 199 (700 – 1751) |
Deficient IgG Subclass(es) | Percentage (n) | Percentage (n) |
1, 3 | 38.6 (44) | 8.7 (11) |
1 | 16.7 (19) | 17.5 (22) |
1, 2, 3 | 12.3 (14) | 0 |
3 | 7.0 (8) | 52.4 (66) |
1, 2 | 7.0 (8) | 0 |
1, 3, 4 | 7.0 (8) | 0 |
1, 4 | 5.3 (6) | 3.2 (4) |
2, 3 | 3.5 (4) | 1.6 (2) |
1, 2, 3, 4 | 2.6 (3) | 0 |
2 | 0.9 (1) | 3.2 (4) |
1, 2, 4 | 0.9 (1) | 0 |
4 | 0 | 7.9 (10) |
3, 4 | 0 | 4.8 (6) |
2, 3, 4 | 0 | 0.8 (1) |
Index Patients with Serum IgA Deficiency, % (n) | 21.1 (24) | 9.5 (12) |
Index Patients with Serum IgM Deficiency, % (n) | 18.4 (21) | 7.9 (10) |
Frequencies of HLA-A and -B Phenotypes
A* Phenotypes | Frequency in CVID and IgGSD Index Patients (n= 240) | Frequency in Control Subjects (n) | Significant Uncorrected Values of p
| Significant Corrected Values of p
2
|
---|---|---|---|---|
01 | 0.3458 | 0.3397 (1,319) | ||
02 | 0.5292 | 0.5206 (1,310) | ||
03 | 0.2875 | 0.2739 (1,318) | ||
11 | 0.075 | 0.1136 (1,320) | ||
23 | 0.0500 | 0.0375 (1,254) | ||
24 | 0.300 | 0.1304 (1,265) | < 0.0001 | < 0.0016 |
25 | 0.0333 | 0.0297 (1,281) | ||
26 | 0.0500 | 0.0634 (1,278) | ||
28 | 0.025 | 0.0773 (1,320) | ||
29 | 0.0583 | 0.0620 (1,290) | ||
30 | 0.0292 | 0.0405 (1,308) | ||
31 | 0.0542 | 0.0350 (1,258) | ||
32 | 0.0375 | 0.0536 (1,232) | ||
33 | 0.0083 | 0.0176 (1,248) | ||
34 | 0.0083 | 0.0044 (1,146) | ||
66 | 0.0167 | 0 (243) |
B* Phenotypes | Frequency in CVID and IgGSD Index Patients (n = 240) | Frequency in Control Subjects (n) | Significant Uncorrected Values of p
| Significant Corrected Values of p
2
|
---|---|---|---|---|
07 | 0.2667 | 0.2259 (1,321) | ||
08 | 0.2583 | 0.2487 (1,315) | ||
13 | 0.0250 | 0.0343 (1,314) | ||
14 | 0.1167 | 0.0639 (1,314) | 0.0037 | |
15 | 0.0792 | 0.0144 (1,320) | < 0.0001 | < 0.0030 |
18 | 0.0708 | 0.0775 (1,251) | ||
27 | 0.0708 | 0.0895 (1,318) | ||
35 | 0.0917 | 0.1406 (1,309) | 0.0403 | |
37 | 0.0250 | 0.0240 (1,167) | ||
38 | 0.0167 | 0.0193 (1,194) | ||
39 | 0.0250 | 0.0225 (1,198) | ||
40 | 0.0792 | 0.0265 (1,321) | < 0.0001 | < 0.0030 |
41 | 0.0167 | 0.0119 (1,089) | ||
42 | 0.0042 | 0.0040 (1,252) | ||
44 | 0.3167 | 0.2866 (1,263) | ||
45 | 0.0083 | 0.0177 (1,241) | ||
46 | 0.0042 | 0 (19) | ||
47 | 0.0083 | 0.0039 (513) | ||
48 | 0.0042 | 0 (909) | ||
49 | 0.0417 | 0.0171 (1,230) | 0.0153 | |
50 | 0.0333 | 0.0140 (1,212) | 0.0414 | |
51 | 0.1042 | 0.0696 (1,250) | ||
52 | 0.0167 | 0.0180 (1,164) | ||
53 | 0.0083 | 0.0077 (1,163) | ||
54 | 0 | 0.0058 (1,027 | - - - | |
55 | 0.0208 | 0.0259 (1,042) | ||
56 | 0.0125 | 0.0097 (928) | ||
57 | 0.0667 | 0.0385 (1,014) | ||
58 | 0.0042 | 0.0256 (1,014) | 0.0228 | |
60 | 0.0583 | 0.1206 (1,086) | ||
61 | 0.0167 | 0.0173 (980) | ||
62 | 0.0333 | 0.1285 (1,175) | < 0.0001 | < 0.0030 |
78 | 0.0042 | no data | - - - |
Frequencies of HLA-A and -B Haplotypes
HLA-A | HLA-B | Frequency in 195 CVID and IgGSD Index Cases (390 chromosomes) | Frequency in 751 Controls (1502 chromosomes) | Significant Uncorrected Values of p
| Significant Corrected Values of p
1
|
---|---|---|---|---|---|
01 | 08 | 0.1308 | 0.0925 | 0.0252 | |
02 | 44 | 0.1385 | 0.0633 | < 0.0001 | < 0.0085 |
60 | 0.0103 | 0.0233 | 0.0076 | ||
03 | 07 | 0.1000 | 0.0546 | 0.0011 | |
14 | 0.0231 | 0.0113 | 0.0095 | ||
44 | 0 | 0.0127 | 0.0122 | ||
31 | 40 | 0.0103 | 0.0013 | 0.0187 | |
32 | 14 | 0.0077 | 0 | 0.0087 |
First Haplotype | Second Haplotype | Frequency of Haploidentical Index Cases (n) |
---|---|---|
A*01-B*08 | A*02-B*27 | 0.0154 (3) |
A*02-B*44 | 0.0256 (5) | |
A*03-B*07 | 0.0205 (4) | |
A*23-B*44 | 0.0103 (2) | |
A*29-B*44 | 0.0103 (2) | |
A*30-B*13 | 0.0103 (2) | |
A*32-B*14 | 0.0103 (2) | |
A*02-B*07 | A*03-B*07 | 0.0154 (3) |
A*02-B*18 | A*02-B*44 | 0.0103 (2) |
A*02-B*44 | A*02-B*44 | 0.0205 (4) |
A*02-B*60 | 0.0103 (2) | |
A*03-B*07 | 0.0205 (4) | |
A*03-B*14 | 0.0103 (2) | |
A*25-B*18 | 0.0103 (2) | |
A*31-B*40 | 0.0103 (2) | |
A*03-B*07 | A*03-B*07 | 0.0103 (2) |
A*24-B*44 | 0.0103 (2) | |
A*29-B*44 | 0.0154 (3) | |
A*24-B*07 | A*29-B*18 | 0.0103 (2) |
A*24-B*60 | A*28-B*60 | 0.0103 (2) |
Segregation of HLA Haplotypes with CVID or IgGSD in Kinships
Relationships of HLA Phenotypes and Haplotypes to Immunoglobulin Phenotypes
Comparison of HLA-A and -B Phenotype Frequencies in CVID and IgGSD
Comparison of Haplotype Frequencies in CVID and IgGSD
Possible Dose Effect of Haplotype on Total Serum Immunoglobulin Concentrations
Number of Significantly Associated Haplotypes | 0 | 1 | 2 |
---|---|---|---|
Serum IgG, mg/dL (n) | 734 ± 273 (45) | 735 ± 287 (112) | 749 ± 257 (33) |
Serum IgA, mg/dL (n) | 167 ± 92 (48) | 157 ± 117 (109) | 169 ± 71 (33) |
Serum IgM, mg/dL (n) | 108 ± 70 (46) | 116 ± 96 (110) | 115 ± 108 (34) |
Frequencies of Index Patients with HLA Haplotype A*01-B*08
Serum Immunoglobulin Concentrations | Total IgG Concentration, frequency in 195 Index Cases (fraction) | IgA Concentration, frequency in 195 Index Cases (fraction) | IgM Concentration, frequency in 195 Index Cases (fraction) |
---|---|---|---|
No Deficiency2
| 0.23 (23/100) | 0.24 (39/162) | 0.24 (41/169) |
Deficiency2
| 0.27 (26/95) | 0.30 (10/33) | 0.31 (8/26) |