Complement system is a humoral recognition and effector system comprised of hepatically synthesized plasma proteins that play a role in innate immunity and inflammation.
Rare (1-7%) primary immunodeficiency syndrome
Relative distribution of the primary immunodeficiencies according to a more traditional classification. | Stiehm ER, editor. Immunologic disorders in infants and children. 5th ed. Philadelphia: Elsevier, Inc.; 2004
Classification
Early complement deficiencies (C1-C4):
Increased risk of severe, recurrent pyogenic sinus and respiratory tract infections
Increased risk of SLE
C2 deficiency (M/C complement deficiency)
Terminal complement deficiencies (C5–C9):
Increased susceptibility to recurrent Neisseria bacteremia
Complement regulatory protein deficiencies:
C1 esterase inhibitor deficiency
Causes hereditary angioedema due to unregulated activation of kallikrein → ↑ bradykinin.
Characterized by ↓ C4 levels
ACE inhibitors contraindicated
Paroxysmal nocturnal hemoglobinuria
A defect in the PIGA gene preventing the formation of anchors for complement inhibitors, such as decay-accelerating factor (DAF/CD55) and membrane inhibitor of reactive lysis (MIRL/CD59)
Causes complement-mediated lysis of RBCs
(2020) Inherited Innate Immunodeficiencies (Immunology) Flashcards | Memorang. Retrieved February 07, 2020, from https://www.memorangapp.com/flashcards/29949/Inherited+Innate+Immunodeficiencies/
Aetiology
Bacteriology of microorganisms involved in complement deficiencies. | Audemard-Verger, A., Descloux, E., Ponard, D., Deroux, A., Fantin, B., Fieschi, C., … Bienvenu, B. (2016). Infections Revealing Complement Deficiency in Adults: A French Nationwide Study Enrolling 41 Patients. Medicine, 95(19), e3548–e3548. https://doi.org/10.1097/MD.0000000000003548
A Variety Of. (2018) Introduction to immunology | McMaster Pathophysiology Review. Retrieved May 14, 2018, from http://www.pathophys.org/immunology/Schematic representing the activation of the complement cascade. The fragments released into solution are indicated in blue. The key fluid-phase regulators are indicated in green. | Ab, antibody; CRP, C-reactive protein; SAP, serum amyloid P component; PTX3, pentraxin 3; C1 inh, C1 inhibitor; α2-M, α2-macroglobulin; C4BP, C4b-binding protein; FHL-1, factor H-like protein-1; FHR-1, factor H-related molecule-1. | Ram, S., Lewis, L. A., & Rice, P. A. (2010). Infections of people with complement deficiencies and patients who have undergone splenectomy. Clinical Microbiology Reviews, 23(4), 740–780. https://doi.org/10.1128/CMR.00048-09
C4b, C3b → Opsonization
C3a, C5a → Inflammation
Clinical features
Recurrent infections:
Clinical manifestations of infections. | Audemard-Verger, A., Descloux, E., Ponard, D., Deroux, A., Fantin, B., Fieschi, C., … Bienvenu, B. (2016). Infections Revealing Complement Deficiency in Adults: A French Nationwide Study Enrolling 41 Patients. Medicine, 95(19), e3548–e3548. https://doi.org/10.1097/MD.0000000000003548
Other manifestations:
Auto-immune disorders
Glomerulonephritis
Joint problems (manifestation)
Lung function (MBL variant alleles)
Angioedema
Dermatomyositis
Vasculitis
Anaphylactoid purpura
SLE patients with a homozygous deficiency of early components for the classical pathway of complement activation: Severe cutaneous lesions are common clinical presentations in SLE patients with a complete complement deficiency. (A) A homozygous C1q-deficient male child with cutaneous infection (upper panel) and with discoid lupus erythematosus and scarring lesions on face when he was 22 years old (lower panel). (B) A male child with discoid lupus at 16-month old with homozygous C1r-deficiency. This patient experienced generalized seizures, developed a scissoring gait with toe walking, spasticity and weakness of the legs. At 18 years old, he was diagnosed with class IV lupus nephritis and progressed to end-stage renal disease. (C) A complete C4-deficient girl at 3 years old with butterfly rash and cheilitis (upper panel), and osteomyelitis of the femur at 10 years old (lower panel). This patient died at age 12 because of pulmonary infection and cardiovascular failure. (D) A homozygous C2-deficient young woman with acute cutaneous lupus erythematosus. The upper panel shows the butterfly rash, and the lower panel shows photosensitive lesions on sun-exposed areas | Lintner, K. E., Wu, Y. L., Yang, Y., Spencer, C. H., Hauptmann, G., Hebert, L. A., … Yu, C. Y. (2016). Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases. Frontiers in immunology, 7, 36. doi:10.3389/fimmu.2016.00036
