Table 1.

Clinical and laboratory features in patients with heterozygous NFKB2 mutations

ID NFKB2 mutationA1 (p.E418X)A2 (p.E418X)B1 (p.R635X)B2 (p.R635X)B3* (p.R635X)C1 (p.S866R)
Age, y/sex 28/M 63/M 33/F 28/M 20/M 14/M 
Abs no. of lymphocytes, ×109/L 0.308 1.05 6.14 2.371 n.a 4.96 
CD3+, abs no., ×109/L (%) 0.25 (82) 0.822 (78) 5.845 (95) 2.284 (96) (36) 4.494 (90.6) 
CD4+/CD3+, ×109/L (%) 0.17 (58) 0.684 (65) 0.792 (12.9) 0.423 (18) 7.3 2.981 (60.1) 
CD62L+/CD45RA+, ×109/L (%) 0.043 (12.7) 0.189 (18) 0.172 (2.8) n.a n.a 2.252 (45.4) 
CD62L+/CD45RA−, ×109/L (%) 0.14 (41.1) 0.376 (35.8) 0.381 (6.2) n.a n.a 0.397 (8) 
CD62L−/CD45RA−, ×109/L (%) 0.03 (8.7) 0.117 (11.1) 0.233 (3.8) n.a n.a 0.084 (1.7) 
CD62L−/CD45RA+, ×109/L (%) 0 (0) 0.002 (0.2) 0.006 (0.1) n.a n.a 0.248 (5) 
CD8+/CD3+, ×109/L (%) 0.07 (23.6) 0.105 (10) 4.937 (80.4) 1.843 (77.7) (12.8) 1.235 (24.9) 
CD62L+/CD45RA+, ×109/L (%) 0.052 (15.2) 0.044 (4.2) 1.345 (21.9) n.a n.a 0.957 (19.3) 
CD62L+/CD45RA−, ×109/L (%) 0.019 (5.5) 0.024 (2.3) 0.141 (2.3) n.a n.a 0.02 (0.4) 
CD62L−/CD45RA−, ×109/L (%) 0.008 (2.3) 0.027 (2.6) 0.393 (6.4) n.a n.a 0.04 (0.8) 
CD62L−/CD45RA+, ×109/L (%) 0.003 (0.9) 0.011 (1) 3.058 (49.8) n.a n.a 0.218 (4.4) 
CD19+, abs no., ×109/L (%) 0.02 (6) 0.154 (14.7) 0.018 (0.3) 0.02 (0.8) (33.7) 0.308 (6.2) 
CD19+/CD38+: ×109/L (%) 0.02 (6) 0.143 (13.6) n.a n.a n.a 0.298 (6) 
CD19+/CD27+/IgM+, ×109/L (%) 0 (0) 0.005 (0.5) n.a n.a n.a 0 (0) 
CD19+/CD27+/IgM−, ×109/L (%) 0 (0) 0.001 (0.1) n.a n.a n.a 0.005 (0.1) 
NK cells, abs no., ×109/L (%) 0.02 (6.5) 0.075 (7.1) 0.258 (4.2) 0.064 (2.7) (30) 0.188 (3.8) 
CD3+/CD4+/RA+/CD31+,* % 5.9 4.4 1.5 1.9 1.9 37.7 
CD3+/CD4+/RA−/CXCR5+,* % 4.2 0.3 0.1 0.5 0.5 0.5 
CD4+/CD3+ Vβ spectratyping* Normal distribution Normal distribution Normal distribution Normal distribution Normal distribution Normal distribution 
CD8+/CD3+ Vβ spectratyping* Normal distribution Normal distribution Vβ 22 expansion in CD8 cells Normal distribution Normal distribution Normal distribution 
Lymphocyte proliferations†       
 Mitogens and antigens PHA <20% n.a PHA <50% PHA normal n.a PHA normal 
ConA <20% ConA <50% ConA normal ConA normal 
PWM <20% PWM normal PWM normal PWM normal 
Tetanus <1% Tetanus normal Tetanus normal 
Candida <1%      
Immunoglobulins, g/L       
 IgG 1.95‡,§ n.a 14.44‡ 2.65 n.a 2.41 
 IgA <0.01 n.a <0.01 <0.02 n.a 0.1 
 IgM <0.01 n.a 0.22 0.24 n.a 0.23 
Vaccine responses       
 Not tested; on IgG replacement Not tested Poor response to pneumococcal polysaccharide vaccination Not tested Not tested Protective titers to hepatitis A, tetanus and diphteria toxoids, HiB, and pneumococcal polysaccharide vaccination 
Clinical history       
 Recurrent sinusitis and pneumonias; splenomegaly;
thrombocytopenia; lymphadenopathy; lymphopenia; primary sclerosing cholangitis 		Asymptomatic until the age of 48 y; rheumatoid arthritis T-LGL leukemia (with red cell aplasia); T-cell lymphocytosis; lymphocytic interstitial pneumonitis; bronchiolitis obliterans; bronchiectasis; onychomycosis; esophageal candidiasis; warts;
recurrent herpes labialis; HPV cervical intraepithelial neoplasia; EBV viremia; CMV viremia; chronic diarrhea; splenomegaly (s/p splenectomy); basal cell carcinomas 		Recurrent sinusitis, otitis, and pneumonias; Pj pneumonia; bronchiectasis; recurrent thrush; warts; mild microcytic anemia; mild thrombocytopenia;
splenomegaly; chronic diarrhea (not infectious) 		Asymptomatic Spontaneously controlled molluscum contagiosum; ACTH deficiency; GH deficiency 
ID NFKB2 mutationA1 (p.E418X)A2 (p.E418X)B1 (p.R635X)B2 (p.R635X)B3* (p.R635X)C1 (p.S866R)
Age, y/sex 28/M 63/M 33/F 28/M 20/M 14/M 
Abs no. of lymphocytes, ×109/L 0.308 1.05 6.14 2.371 n.a 4.96 
CD3+, abs no., ×109/L (%) 0.25 (82) 0.822 (78) 5.845 (95) 2.284 (96) (36) 4.494 (90.6) 
CD4+/CD3+, ×109/L (%) 0.17 (58) 0.684 (65) 0.792 (12.9) 0.423 (18) 7.3 2.981 (60.1) 
CD62L+/CD45RA+, ×109/L (%) 0.043 (12.7) 0.189 (18) 0.172 (2.8) n.a n.a 2.252 (45.4) 
CD62L+/CD45RA−, ×109/L (%) 0.14 (41.1) 0.376 (35.8) 0.381 (6.2) n.a n.a 0.397 (8) 
CD62L−/CD45RA−, ×109/L (%) 0.03 (8.7) 0.117 (11.1) 0.233 (3.8) n.a n.a 0.084 (1.7) 
CD62L−/CD45RA+, ×109/L (%) 0 (0) 0.002 (0.2) 0.006 (0.1) n.a n.a 0.248 (5) 
CD8+/CD3+, ×109/L (%) 0.07 (23.6) 0.105 (10) 4.937 (80.4) 1.843 (77.7) (12.8) 1.235 (24.9) 
CD62L+/CD45RA+, ×109/L (%) 0.052 (15.2) 0.044 (4.2) 1.345 (21.9) n.a n.a 0.957 (19.3) 
CD62L+/CD45RA−, ×109/L (%) 0.019 (5.5) 0.024 (2.3) 0.141 (2.3) n.a n.a 0.02 (0.4) 
CD62L−/CD45RA−, ×109/L (%) 0.008 (2.3) 0.027 (2.6) 0.393 (6.4) n.a n.a 0.04 (0.8) 
CD62L−/CD45RA+, ×109/L (%) 0.003 (0.9) 0.011 (1) 3.058 (49.8) n.a n.a 0.218 (4.4) 
CD19+, abs no., ×109/L (%) 0.02 (6) 0.154 (14.7) 0.018 (0.3) 0.02 (0.8) (33.7) 0.308 (6.2) 
CD19+/CD38+: ×109/L (%) 0.02 (6) 0.143 (13.6) n.a n.a n.a 0.298 (6) 
CD19+/CD27+/IgM+, ×109/L (%) 0 (0) 0.005 (0.5) n.a n.a n.a 0 (0) 
CD19+/CD27+/IgM−, ×109/L (%) 0 (0) 0.001 (0.1) n.a n.a n.a 0.005 (0.1) 
NK cells, abs no., ×109/L (%) 0.02 (6.5) 0.075 (7.1) 0.258 (4.2) 0.064 (2.7) (30) 0.188 (3.8) 
CD3+/CD4+/RA+/CD31+,* % 5.9 4.4 1.5 1.9 1.9 37.7 
CD3+/CD4+/RA−/CXCR5+,* % 4.2 0.3 0.1 0.5 0.5 0.5 
CD4+/CD3+ Vβ spectratyping* Normal distribution Normal distribution Normal distribution Normal distribution Normal distribution Normal distribution 
CD8+/CD3+ Vβ spectratyping* Normal distribution Normal distribution Vβ 22 expansion in CD8 cells Normal distribution Normal distribution Normal distribution 
Lymphocyte proliferations†       
 Mitogens and antigens PHA <20% n.a PHA <50% PHA normal n.a PHA normal 
ConA <20% ConA <50% ConA normal ConA normal 
PWM <20% PWM normal PWM normal PWM normal 
Tetanus <1% Tetanus normal Tetanus normal 
Candida <1%      
Immunoglobulins, g/L       
 IgG 1.95‡,§ n.a 14.44‡ 2.65 n.a 2.41 
 IgA <0.01 n.a <0.01 <0.02 n.a 0.1 
 IgM <0.01 n.a 0.22 0.24 n.a 0.23 
Vaccine responses       
 Not tested; on IgG replacement Not tested Poor response to pneumococcal polysaccharide vaccination Not tested Not tested Protective titers to hepatitis A, tetanus and diphteria toxoids, HiB, and pneumococcal polysaccharide vaccination 
Clinical history       
 Recurrent sinusitis and pneumonias; splenomegaly;
thrombocytopenia; lymphadenopathy; lymphopenia; primary sclerosing cholangitis 		Asymptomatic until the age of 48 y; rheumatoid arthritis T-LGL leukemia (with red cell aplasia); T-cell lymphocytosis; lymphocytic interstitial pneumonitis; bronchiolitis obliterans; bronchiectasis; onychomycosis; esophageal candidiasis; warts;
recurrent herpes labialis; HPV cervical intraepithelial neoplasia; EBV viremia; CMV viremia; chronic diarrhea; splenomegaly (s/p splenectomy); basal cell carcinomas 		Recurrent sinusitis, otitis, and pneumonias; Pj pneumonia; bronchiectasis; recurrent thrush; warts; mild microcytic anemia; mild thrombocytopenia;
splenomegaly; chronic diarrhea (not infectious) 		Asymptomatic Spontaneously controlled molluscum contagiosum; ACTH deficiency; GH deficiency 

Numbers/terms in italics/bold indicate values above/below the normal range, respectively, compared with age-matched controls.

Abs no., absolute number; ACTH, adrenocorticotropic hormone; CMV, cytomegalovirus; ConA, concanavalin A; EBV, Epstein-Barr virus; F, female; GH, growth hormone; HiB, H influenzae B; HPV, human papillomavirus; ID, identification; M, male; n.a, data not available; NK, natural killer; PBMC, peripheral blood mononuclear cell; PHA, phytohemagglutinin; Pj, P jirovecii; PWM, pokeweed mitogen; s/p, status post; T-LGL, T-cell large granular lymphocyte.

*

Tested on frozen PBMCs.

†

In percentage values when compared with the healthy control normal ranges at the center the study was performed.

‡

On IgG replacement therapy.

§

Partial adherence to therapy.

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