Acquired deficiencies of the complement system
- M Kathryn Liszewski, PhD
M Kathryn Liszewski, PhD
- Assistant Professor of Medicine
- Washington University School of Medicine
- John P Atkinson, MD
John P Atkinson, MD
- Samuel B Grant Professor of Medicine
- Professor of Molecular Microbiology
- Chief, Division Rheumatology
- Washington University School of Medicine
- Section Editors
- Jordan S Orange, MD, PhD
Jordan S Orange, MD, PhD
- Section Editor — Immunology and Immunodeficiency
- Professor of Pediatrics
- Chief of Immunology, Allergy, and Rheumatology
- Baylor College of Medicine
- Texas Children's Hospital
- Peter H Schur, MD
Peter H Schur, MD
- Editor-in-Chief — Rheumatology
- Section Editor — Basic Science
- Professor of Medicine
- Harvard Medical School
Deficiencies in complement proteins may be inherited or acquired (secondary). Secondary causes of complement deficiency will be presented in this topic review. Inherited disorders of the complement system, as well as a description of the complement pathways and the clinical evaluation of complement, are presented separately. (See "Inherited disorders of the complement system" and "Complement pathways" and "Overview and clinical assessment of the complement system".)
Acquired deficiencies in complement proteins are more common than inherited complement disorders. Reductions in complement secondary to acquired disease processes are usually only partial and affect several complement components at once. As an example, approximately 50 percent of patients with systemic lupus erythematosus (SLE) will have reductions in C4 and C3, reflecting classical pathway activation.
These acquired complement deficiencies are most commonly encountered in diseases featuring autoantibodies. In many diseases, such as milder forms of SLE, augmented hepatic synthesis of components may be sufficient to maintain the levels in the normal range. The management of most disorders of the complement system featuring excessive activation focuses on the treatment of the underlying disorders.
Challenges in interpretation — One problem clinicians may encounter when managing disorders featuring acquired deficiencies of complement components is that the predisease levels of proteins, such as C3, are rarely known. For example, the "normal" laboratory range of C3 in the population is from 80 to 160 mg/dL. A 17-year-old female with new-onset SLE may present with a C3 value of 92 mg/dL. Although this is considered in the "normal range," if her post-treatment C3 value rises to 125 mg/dL in six weeks, then her predisease value was at least this or higher. Even at 125 mg/dL, a C3 turnover study or assessment of complement split products might show mildly accelerated consumption. Measuring C4, which commonly parallels changes in C3 levels, is more complicated because of C4 copy number, which is discussed elsewhere. Thus, complement levels need to be interpreted in the context of the clinical setting. (See "Inherited disorders of the complement system", section on 'C4 deficiency'.)
MECHANISMS OF ACQUIRED COMPLEMENT DISORDERS
Acquired deficiencies in complement proteins may result from several mechanisms:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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- Challenges in interpretation
- MECHANISMS OF ACQUIRED COMPLEMENT DISORDERS
- INCREASED CONSUMPTION BY IMMUNE COMPLEXES
- Systemic lupus erythematosus
- Antiphospholipid syndrome
- Vasculitic syndromes
- Renal diseases
- - C3 nephritic factor
- - Dense deposit disease
- - C3 glomerulopathy
- - C4 nephritic factor
- Autoimmune hemolytic anemia
- IgG4–positive multiorgan lymphoproliferative syndrome
- Viral infections
- Acquired angioedema
- REDUCED HEPATIC SYNTHESIS
- LOSS OF COMPLEMENT COMPONENTS IN THE URINE