STEPTRACKERIMMUNOLOGY + HEMATOLOGY | IMMUNODEFICIENCY | HIGH-YIELD REVIEW

Phagocyte & Complement Deficiencies

Phagocyte defects give bacterial and fungal abscesses of skin, lung and lymph nodes; complement defects give encapsulated infections, Neisseria or lupus-like disease depending on which step is missing.

FOCUS ON
Phagocytes: LAD type 1 (CD18, AR) — delayed cord separation (> 30 days), omphalitis, no pus, marked neutrophilia; CGD (NADPH oxidase, X-linked most) — abscesses and granulomas from catalase ⁺ organisms (S aureus, Serratia, Burkholderia, Nocardia, Aspergillus); abnormal DHR flow → TMP-SMX + itraconazole prophylaxis, IFN-γ, HSCT; Chédiak-Higashi (LYST, AR) — giant granules, partial albinism, neuropathy, bleeding, HLH; MPO deficiency — usually mild, Candida; severe congenital neutropenia (ELANE). Complement: C1q/C2/C4 → SLE-like; C3 → severe pyogenic infections; C5–C9 → Neisseria; properdin → Neisseria; C1-INH → hereditary angioedema; DAF/CD59 → PNH.
DISORDER
DEFECT
FINDINGS
DIAGNOSIS · TREATMENT
Leukocyte adhesion deficiency 1
CD18 (β2 integrin), AR
Delayed umbilical cord separation, omphalitis, skin/mucosal infections without pus, periodontitis, neutrophilia
Flow: ↓ CD18 · HSCT
Chronic granulomatous disease
NADPH oxidase (gp91phox X-linked; p47phox AR)
Recurrent abscesses (skin, lung, liver, nodes), osteomyelitis, granulomas obstructing GI/GU tract
Abnormal DHR (NBT negative) · TMP-SMX, itraconazole, IFN-γ · HSCT
Chédiak-Higashi syndrome
LYST, AR → microtubule/lysosomal trafficking failure
Recurrent pyogenic infections, partial oculocutaneous albinism, peripheral neuropathy, bleeding, HLH ("accelerated phase")
Giant granules in neutrophils · HSCT
Myeloperoxidase deficiency
MPO, AR; most common phagocyte defect
Usually asymptomatic; Candida infections (diabetes)
Normal DHR · absent MPO staining
Severe congenital neutropenia · cyclic neutropenia
ELANE and others
Severe bacterial infections, oral ulcers (cyclic every ~21 days)
G-CSF · leukemia risk
Early classical (C1q, C1r/s, C2, C4)
Poor immune-complex and apoptotic clearance
SLE-like disease, encapsulated infections
↓ CH50
C3 deficiency
No opsonization, no downstream activation
Severe recurrent pyogenic infections, immune-complex GN
↓ CH50 and AH50
C5–C9 · properdin
No MAC
Recurrent Neisseria meningitidis and disseminated gonococcal infection
Meningococcal vaccines · same risk with eculizumab
C1 esterase inhibitor deficiency
AD; uncontrolled kallikrein → bradykinin
Hereditary angioedema: non-itchy swelling, abdominal pain attacks, laryngeal edema
↓ C4 · C1-INH concentrate, icatibant · no ACE inhibitors
DAF (CD55) / CD59 loss
Acquired PIGA mutation (GPI anchor)
PNH: intravascular hemolysis, thrombosis (hepatic veins), pancytopenia
Flow cytometry (FLAER) · eculizumab
Factor H · factor I deficiency
Uncontrolled alternative pathway
Atypical HUS, C3 glomerulopathy; ↓ C3
Eculizumab
MBL deficiency
Lectin pathway
Infections in infancy, usually mild
Common polymorphisms

Mechanism — catalase and CGD

No NADPH oxidase
→
Neutrophil borrows microbe's H₂O₂For MPO → HOCl
→
Catalase ⁺ microbes break down their H₂O₂
→
Survive in phagosome → granulomas, abscesses

Complement level patterns

DEFICIENCY
CH50
AH50
INFECTION / DISEASE
C1q, C2, C4
↓
Normal
SLE-like, encapsulated
C3
↓
↓
Severe pyogenic
C5–C9
↓
↓
Neisseria
Factor B, D, properdin
Normal
↓
Neisseria

How it's tested

COMMON CONFUSIONCGD (abnormal DHR, catalase ⁺ abscesses) vs MPO deficiency (normal DHR, mostly benign) — both affect the same killing pathway at different steps.
THE TRAPA patient with recurrent meningococcal disease needs a CH50/AH50 workup — and any patient starting eculizumab needs meningococcal vaccines.
YOUR APPROACHAbscesses or no pus (phagocyte) vs encapsulated/Neisseria/lupus-like (complement) → screening test (DHR, CD18 flow, CH50/AH50) → specific defect.

If you see… think…

Umbilical cord still attached at 5 weeks → LAD type 1
Boy with Serratia abscess and Aspergillus pneumonia → CGD
Screening test for CGD → DHR flow cytometry
Silvery hair, giant neutrophil granules, neuropathy → Chédiak-Higashi
Diabetic with Candida and normal DHR → MPO deficiency
Oral ulcers and fevers every 3 weeks → cyclic neutropenia
Recurrent Neisseria, low CH50 and AH50 → terminal complement deficiency
Lupus-like disease in a child with normal anti-dsDNA → early complement deficiency
Episodic non-itchy swelling, low C4 → C1-INH deficiency
Hemolysis, Budd-Chiari and pancytopenia → PNH