TABLE I.
Clinical information and immunoglobulin levels on patients with mutations*
Patient no. | Sex | Age (y) | Mutation | Clinical | IgG§ | IgA | IgM |
---|---|---|---|---|---|---|---|
1 | F | 62 | C104R | ITP*, splenomegaly, splenectomy | 251 | <6 | 27 |
2 | M | 46 | C172Y | Frequent URI, chronic otitis media, hearing loss | 490 | 18 | 33 |
3 | F | 44 | C104R S194X |
AIHA/Coombs positive anemia ×3, ITP ×3; numerous pneumonias; pulmonary infiltrates, splenomegaly; splenectomy | 200 | <6 | 24 |
4 | F | 44 | L171R A181E |
URIs, arthritis, Sweet syndrome, pneumonia, aseptic meningitis | 392 | 59 | 6 |
5 | F | 58 | C104R S144X |
Urticaria and angioedema, allergies/joint pain | 332 | 48 | 14 |
6 | F | 66 | A181E | Juvenile RA, rheumatic fever, microscopic colitis pneumonia, sinusitis, otitis, cardiac valve replacement, lymphadenopathy, splenomegaly, ITP, anti-IgA Ab | 594 | <7 | 34 |
7 | F | 43 | C104R | Seizure disorder, colitis, sinusitis | 164 | <5 | 5 |
8 | F | 50 | R72H | Recurrent URI, sinusitis, pneumonia, breast cancer | 293 | 110 | 90 |
9 | M‡ | 45 | C104R | ITP, pan-sinusitis, pneumonia ×4; granulomatous skin disease | <7 | <7 | 6 |
10 | F | 41 | C104R | ITP, lymphadenopathy, granulomatous infiltrates, neutropenia, splenomegaly, splenectomy | 475 | 47 | 54 |
11 | F | 17 | A181E | Sinusitis, myringotomy tubes | 371 | 14 | 4 |
12 | F | 26 | A181E | Granulomatous lesions skin, lungs: fibronodular infiltrates, arthritis, ITP, splenomegaly, splenectomy, diarrhea/uveitis AIHA/Coombs positive anemia | 164 | 5 | 20 |
13 | F | 67 | C104R | Chronic sinusitis, bronchitis, chronic rectal herpes simplex | 530 | 11 | <5 |
Of the 176 subjects with CVID, 30 (17%) had an exon five P251L single nucleotide polymorphism (SNP), and 7 others had V220A SNP, both found previously in normal subjects. In 2 of the subjects with CVID, the P251L SNP was homozygous. (These subjects are not considered further here.)
ITP, Immune thrombocytopenia purpura; AIHA, autoimmune hemolytic anemia; F, female; JRA, juvenile rheumatoid arthritis; M, male; ND, not done; RA, rheumatoid arthritis; URI, upper respiratory tract infections.
X-linked agammaglobulinemia excluded by genetic analysis of Btk.
Before immunoglobulin replacement: serum immunoglobulins (mg/dL); normal ranges for adults: IgG, 694–1618; IgA, 81–463; IgM, 48–271 mg/dL; IgG1, 344–966; IgG2,133–622; IgG3,12–138; IgG4, 1–115 mg/dL.