Table 2.
Common and rarely reported infections in predominantly antibody deficiencies.
| Disease (inheritance) | Gene | Bacterial infections | Viral infections | Fungal/protozoal infections | Other infections reported rarely* |
|---|---|---|---|---|---|
| Severe reduction in all serum immunoglobulin isotypes with profoundly decreased or absent B cells, agammaglobulinemia | |||||
| X-linked agammaglobulinemia (XLA) | |||||
| Bruton agammaglobulinemia | BTK | Respiratory tract infections with H. influenza, S. pneumonia, Pseudomonas spp, Staphylococcus spp, H. parahemolytica, H. parainfluenza, Klebsiella spp (5–8). Gastrointestinal infections with Campylobacter, Salmonella spp, C difficile, H.pylori, Shigella spp, Flexispira ( 5–8 ). Meningitis/sepsis with S. pneumonia, H. influenza type b (5, 6) Skin infections by S. aureus (6) Septic arthritis by Mycoplasma, Ureaplasma ( 9) |
Gastrointestinal infections with Rotavirus, Enterovirus (5) Vaccine-associated polio, encephalitis with ECHO 11, Coxsackie (5, 7) Hepatitis C (5, 6) Skin infections caused by Herpesvirus (6) |
Gastrointestinal infections with Giardia, Blastocistis hominis (5, 6) Skin infections caused by Candida sp (6) |
Disseminated infection by Spiroplasma apis (10), Achromobacter xylosoxidans sepsis (11), Morganella morganii pericarditis (12), Systemic infection by Aichi virus (13), Infective endocarditis by Enterococcus faecalis (14) Sepsis by Pseudomonas (7) Skin infections by non-H. pylori helicobacter (NHPH) (15) |
| Autosomal recessive agammaglobulinemia | |||||
| µ heavy chain deficiency | IGHM | Bacterial respiratory infections (16–18) Pseudomonas sepsis (16–18) Chronic diarrhea (18, 19) |
Viral respiratory tract infections (17, 18) Enteroviral encephalitis (16) Vaccine-induced paralytic polio (18, 19) |
Haemophilus influenza arthritis (20) Recurrent perirectal abscesses (16) |
|
| P110δ deficiency | PIK3CD | Recurrent sinopulmonary infections with encapsulated bacteria (21) | Persistent rotavirus enteritis (22) Catheter-associated Klebsiella pneumonia sepsis (22) S. pneumonia sepsis (22) |
||
| P85 deficiency | PIK3R1 | Recurrent sinopulmonary infections with encapsulated bacteria (H. influenza, S. pneumonia) (23), |
Influenza A, CMV (23) Prolonged diarrhea after Rotavirus vaccine |
Campylobacter spp bacteremia, interstitial pneumonia (24) | |
| SLC39A7 (ZIP7) deficiency | SLC39A7 | Early onset infections (25) | |||
| λ5 Deficiency | IGLL1 | Otitis media at 2 months, meningitis caused by Haemophilus (26), bilateral lobar pneumonia at 3 months of age (27) | |||
| Igα deficiency | CD79A | Upper and lower respiratory tract infections, recurrent diarrhea (28) | HHV8 and JC virus encephalitis (29) | ||
| Igβ deficiency | CD79B | Upper and lower respiratory tract infections (30, 31) | Salmonella enteritis (30) | ||
| BLNK deficiency | BLNK | Upper and lower respiratory tract infections (32) | Enteroviral viremia, Pseudomonas sepsis, septic arthritis by Proteus mirabilis (32) | ||
| E47 transcription factor deficiency (AR or AD) | TCF3 | Recurrent pneumonia and meningitis (33, 34) | Chronic diarrhea (34) | ||
| Autosomal dominant agammaglobulinemia | |||||
| Hoffman syndrome/TOP2B deficiency | TOP2B | Recurrent respiratory infections by encapsulated bacteria (35) | Haemophilus influenza meningitis (36) | ||
| Severe reduction in At least 2 serum immunoglobulin isotypes with normal or low B cells, CVID phenotype | |||||
| Common variable immune deficiency with no gene defect specified (CVID) (variable) | Unknown | Respiratory tract infections with H. influenza, S. pneumonia, mycoplasma, Moraxella, Pseudomonas spp, Staphylococcus spp, and Klebsiella pneumonia (37, 38) Gastrointestinal infections caused by Campylobacter sp, Salmonella sp, Clostridium difficile, Escherichia coli (37–39) Meningitis caused by S. pneumonia, N. meningitides, and H. influenza (37, 38) Staphylococcal aureus skin abscesses (37, 38) |
Respiratory infections caused by human rhinovirus (HRV), Adenovirus, respiratory syncytial virus (RSV), seasonal Coronavirus (40, 41) Norovirus (42), CMV (39) Recurrent Herpes zoster, invasive papillomavirus (37, 38) |
Gastrointestinal infections caused by Giardia lamblia (37–39) Blastocistis hominis, | Mycobacterial disease, listeriosis, nocardia, Bacilli-Calmette-Guerin, Molluscum contagiosum, Measles, HIV, severe EBV, systemic adenovirus infection, Kaposi sarcoma, Hepatitis C, Hepatitis B, cerebral toxoplasmosis (37, 38) Gastrointestinal infections caused by Isospora belli (43), cryptosporidium, Cryptococcus, Candida sp, Histoplasmosis visceral mycosis (38) |
| Activated P110 δ syndrome (AD) |
PIK3CD (GoF) PIK3R1 (LoF) |
Recurrent respiratory infections by encapsulated bacteria (21) Staphylococcal skin and dental abscess (21) Clostridium difficile colitis Recurrent conjunctivitis (44) |
Recurrent sinopulmonary infections with viruses, Influenza A (44) Severe and persistent infections with EBV, CMV, HSV, VZV (44–46) |
Chronic mucocutaneous candidiasis (44) | Staphylococcus aureus-related periorbital cellulitis, Pseudomonas aeruginosa septicemia, chronic Giardia intestinalis (44) |
| PTEN deficiency (AD) | PTEN | Recurrent upper respiratory infections (47) | Neonatal group B Streptococcus infection, Pneumocystis jiroveci pneumonia (48) | ||
| TWEAK deficiency (AD) | TNFSF12 | Recurrent upper respiratory infections (49) | Warts (49) | Pneumococcal meningitis, Osteomyelitis (49) | |
| TRNT1 deficiency (AR) | TRNT1 | Upper and lower respiratory tract infections (50) | |||
| NFKB1 deficiency (AD) | NFKB1 | Upper respiratory tract infections with S. Pneumonia, H. Influenzae, P. aeruginosa; Clostridium difficile colitis (51, 52) Bacterial meningitis (52) |
Shingles; vaginal HPV; invasive CMV; EBV (51, 52) | P. jiroveci pneumonia; Mycobacterium avium intracellulare; Giardia (51, 52) | PML (51); Chronic Norovirus, rhinovirus (52) |
| NFKB2 deficiency (AD) | NFKB2 | Upper respiratory tract infections (53) | Recurrent HSV skin infections, severe VZV, molluscum, EBV, CMV infections (53) | Pneumocystis jiroveci, Giardia, oral candidiasis (53) | Toxoplasmosis; onycomycosis; Salmonella (53) |
| IKAROS deficiency (AD) | IKZF1 | Recurrent sinopulmonary infections starting in infancy (54) Sepsis, pneumonia, skin abscess by P. aeruginosa (55) |
Severe RSV bronchiolitis, Adenoviral pneumonia, recurrent HSV, EBV+, HPV genital infections (54, 55) | Pneumocystis jiroveci pneumonia, recurrent oral candidiasis (55) | Lung infection with Klebsiella sp, Aspergillus sp, Mycobacterium avium complex. Pneumococcal meningitis, Cryptosporidial cholangitis, Candida parapsilosis fungemia (55), Enterococcus gallinarum sepsis (56) |
| ATP6AP1 deficiency (XL) | ATP6AP1 | Recurrent respiratory infections starting in infancy (57) | |||
| Mannosyl-oligosaccharide glucosidase deficiency (AR) | MOGS | Bacterial respiratory infections (58) | Urinary tract infection by Escherichia coli, Pneumococcal pneumonia with empyema; Staphylococcus aureus osteomyelitis (58) | ||
| CD19 deficiency (AR) | CD19 | Recurrent upper and lower respiratory tract infections (59) | Pneumococcal meningitis; Chronic gastritis by Heliobacter pylori (59) | ||
| CD81 deficiency (AR) | CD81 | Recurrent respiratory tract infections (60) (1 of 1 reported patient) | |||
| CD20 deficiency (AR) | CD20 | Recurrent upper and lower respiratory tract infections (61) (1 of 1 reported patient) | |||
| CD21 deficiency (AR) | CD21 | Recurrent respiratory tract infections with encapsulated bacteria (62) | |||
| TACI deficiency** (AR or AD) | TNFRSF13B | Recurrent respiratory tract infections (63, 64) | Recurrent viral respiratory infections (64) | Rectal herpes simplex (64) | |
| BAFF receptor deficiency (AR) | TNFRSF13C | Recurrent upper and lower respiratory tract infections (65) | Severe Herpes zoster (65) | ||
| IRF2BP2 deficiency (AD) | IRF2BP2 | Recurrent upper and lower respiratory tract infections (66) | |||
| ARHGEF1 deficiency (AR) | ARHGEF1 | Recurrent upper and lower respiratory tract infections (67) | Recurrent VZV, severe oral HSV (67) | ||
| SH3KBP1 deficiency (XL) | SH3KBP1 | Recurrent upper and lower respiratory tract infections (68) | |||
| SEC61A1 deficiency (AD) | SEC61A1 | Early-onset, severe, bacterial sinopulmonary infections; gastroenteritis (69) | |||
| RAC2 deficiency (AR) | RAC2 | Recurrent sinopulmonary infections (70) | |||
| Severe reduction in serum IgG and IgA with normal/elevated IgM and normal numbers of B cells, hyperIgM phenotype | |||||
| AID deficiency (AR or AD) | AID | Upper and lower respiratory tract infections, skin infections, meningitis (71) | Giardia infections (71) | HSV encephalitis, Hepatitis B (71) | |
| UNG deficiency (AR) | UNG | Upper and lower respiratory tract infections (72) | |||
| MSH6 deficiency (AR) | MSH6 | No recurrent or severe infections reported to date (73) | |||
| INO80 deficiency (AR) | INO80 | Severe and recurrent bacterial respiratory infections (74) | |||
| Isotype, light chain, or functional deficiencies with generally normal numbers of B cells | |||||
| Ig heavy chain mutations and deletions (AR)** | Mutation or deletions at 14q32 | Upper and lower respiratory tract infections | Enteroviral infections | ||
| Kappa chain deficiency (AR)** | IGKC | Upper and lower respiratory tract infections (75) | |||
| Isolated IgG subclass deficiency and IgG subclass deficiency with IgA deficiency ** (IgGSCD) | Unknown | Upper and lower respiratory tract infections with S. pneumoniae, H. influenzae type b, N. meningitides | Upper and lower respiratory tract infections with viruses | ||
| Selective IgA deficiency** (SIAD) | Unknown | Upper and lower respiratory tract infections with S. pneumoniae, H. influenzae; Pharyngitis; urinary tract infections (76, 77) | Upper and lower respiratory tract infections with viruses Stomatitis, herpes labialis (76, 77) |
G. lamblia gastroenteritis (78) | |
| Specific antibody deficiency ** (SPAD) | Unknown | Bacterial upper and lower respiratory tract infections (79) Chronnic otorrhea in children (79, 80) |
Recurrent HSV, S. pneumonia sepsis, recurrent folliculitis (79) | ||
| Transient hypogammaglobulinemia of infancy ** (THI) | Unknown | Upper and lower respiratory tract infections, abscesses, urinary tract infections, meningitis, sepsis (81) | Hepatitis, osteomyelitis, VZV infection (81) | ||
| CARD11 GoF (AD) ** | CARD11 | Recurrent upper and lower respiratory tract infections, cellulitis (82) | M. contagiosum, Chronic EBV, BK virus (82) | S. pneumoniae bacteremia (82) | |
| Selective IgM deficiency ** (SIGMD) | Unknown | Upper and lower respiratory tract infections with S. pneumoniae, H. influenza and viruses (83–85) | Varicella zoster, CMV, aseptic meningitis (85) | G. lamblia, Mycobacterial infection (85) | Sepsis (S. pneumonia, N. Meningitides) aseptic meningitis, Invasive Aspergillus (85, 86) |
AR, autosomal recessive; AD, autosomal dominant; CDG-IIb, congenital glycosylation disorder type IIb; CMV, Cytomegalovirus; EBV, Ebstein-Barr virus; GoF, gain-of-function; LoF, loss-of-function; XL, X-linked.
*Infections reported < 10 cases in relatively common PADs, such as CVID, SIAD, IgGSCD, SPAD, and XLA, and <2 patients in all other PADs.
**These conditions may be asymptomatic.