Table 1.

Clinical and immune function of individuals with hypomorphic NEMO mutation.

Functional or clinical category	Observed deficiency	Percent affected
B cell costimulation/CD40 signaling1	15/16*	94%
Infectious susceptibility2	60/61	98%
bacterial infection	45/52	86%
myobacterial infection	23/52	44%
PCP	4/52	8%
DNA viral infection	11/52	21%
meningitis	12/61	21%
pneumonia	19/61	31%
sepsis/bacteremia	20/61	33%
NK function3	10/10*	100%
TNF Response4	9/11*	82%
Ectodermal dysplasia (ED)5	40/52	77%
hyper IgM6	6/40	15%
hypogammaglobulinemia	24/41	59%
hyper IgA	13/35	37%
hyper IgD	2/5	40%
specific antibody deficiency	18/28	64%
specific Pneumococcal antibody	13/16	81%
IL-1 Response7	6/7*	86 %
TLR Response	9/14*	64%
Auto-immune/Inflammatory disease8	14/66	23%
Lymphedema	5/65	8%
Osteopetrosis	5/65	8%
Small for gestational age9	9/65	14%
Dead	24/66	36%

¹Impaired CD40 signaling by EMSA, reporter assay or ELISA or documented inability to undergo T-cell dependent immunoglobulin class switching or memory B cell development

²Persistent or recurrent infection or life threatening infection.

³Cytotoxicity by standard chromium release assay.

⁴Impaired signaling by EMSA, reporter assay, IκB degradation or ELISA

⁵Absence of eccrine sweat glands, hair and sparse or absent conical teeth.

⁶Hyper IgM phenotype (elevated or normal IgM, low IgG and specific antibody production defect or class switch recombination defect)

⁷Impaired IL-1β or TLR signaling by EMSA, reporter assay, CD62L shedding defect or ELISA

⁸The presence of one or more of the following: sustained elevated serum inflammatory markers, chronic arthritis, autoimmune hemolytic anemia, macrophage activation syndrome, non-infecctious colitis.

⁹Lower than two standard deviations below the average weight for gestational age.

^*These assays were performed on a subset of individuals.