Immune Complex Diseases


Immune complex diseases encompass a diverse group of inflammatory conditions characterised by antigen–antibody deposition and attendant activation of complement. Common manifestations include glomerulonephritis, synovitis and dermal vasculitis. Many patients present with constitutional symptoms and less specific signs. A century of research has elucidated the structure of immunoglobulin, furthered understanding of antigen–antibody‐binding interactions and yielded insights into the biochemistry and disorders of complement. Immune complex formation and complement activation trigger the generation of a vast array of mediators and regulators of inflammation. Understanding the integration of these systems has led to our current conceptual framework of immune complex‐mediated tissue injury. Study of animal models and affected patients has contributed greatly to our current understanding of immune complex disease. Appreciation of the wide clinical spectrum and optimal evaluation of affected patients have evolved in concert with advances in understanding the pathophysiology of immune complex‐mediated diseases, whether serum sickness and systemic lupus erythematosus or human immunodeficiency virus (HIV)‐associated immune complex renal disease and complications of monoclonal antibody therapy.

Key Concepts

  • Immune complex diseases are characterised by antigen–antibody deposition and attendant activation of complement.
  • Understanding the physicochemical basis of antigen–antibody‐binding interactions and complement fixation has been facilitated by advances in biochemistry.
  • Beyond immune complex formation and complement activation, the pathophysiology of immune complex disease involves Fc and complement receptors as well as myriad mediators of inflammation.
  • The clinical spectrum of immune complex disease has broadened from serum sickness, autoimmune‐collagen vascular disease and infectious disease to also encompass complications of HIV infection and therapeutic monoclonal antibody administration.
  • Clinical evaluation of patients with suspected immune complex disease relies heavily on clinical setting, recognition of dermal vasculitis, arthritis and glomerulonephritis and biopsy.

Keywords: inflammation; immune complexes; complement; hypersensitivity; vasculitis; glomerulonephritis; serum sickness; human immunodeficiency virus (HIV); acquired immune deficiency syndrome (AIDS); monoclonal antibody therapy

Figure 1. Antibody molecules bind to their cognate antigens resulting in the formation of immune complexes. Immunoglobulin isotypes IgG (subclasses 1–3) and IgM are particularly effective in the fixation of complement via the C1qrs‐mediated classical pathway.
Figure 2. Development of acute serum sickness in rabbits following a single injection of radiolabelled bovine serum albumin (BSA) as antigen. Disease occurs when large quantities of soluble immune complexes are present in the circulation. Reproduced from Rich © Elsevier.
Figure 3. Hemorrhagic, macular lesions of lower extremity. Biopsy revealed leukocytoclastic vasculitis and immune complex deposition within dermal blood vessel walls. Photograph courtesy of Johann Gudjonsson MD and Emily Smith MD.
Figure 4. Immune complex‐mediated glomerulonephritis. These photomicrographs are from a patient with systemic lupus erythematosus and proliferative lupus nephritis. (a) Haematoxylin‐ and eosin‐stained light micrograph reveals acute glomerulonephritis with intracapillary deposits of fibrin (red areas). (b) Direct immunofluorescence reveals granular C1q deposits throughout glomerulus. (c) Transmission electron micrograph reveals coarse (granular) deposits of latticed antigen–antibody complexes along the basement membrane of the glomerulus. Images provided courtesy of Paul Killen.

Further Reading

Abbas AK, Lichtman AH and Pillai S (2015a) Properties and overview of immune responses. In: Cellular and Molecular Immunology, 8th edn, pp. 2–12. Philadelphia, PA: Saunders Elsevier.

Abbas AK, Lichtman AH and Pillai S (2015b) Hypersensitivity disorders. In: Cellular and Molecular Immunology, 8th edn, pp. 400–409. Philadelphia, PA: Saunders Elsevier.

Abbas AK, Lichtman AH and Pillai S (2015c) The complement system. In: Cellular and Molecular Immunology, 8th edn, pp. 272–288. Philadelphia, PA: Saunders Elsevier.

Germuth FG Jr (1953) A comparative histologic and immunologic study in rabbits of induced hypersensitivity of serum sickness type. The Journal of Experimental Medicine 97: 257–282.

Gros P, Milder FJ and Janssen BJ (2008) Complement driven by conformational changes. Nature Reviews Immunology 8: 48–58.

Hardy DJ, Singh AP and deShazo RD (2009) Immune complex disease. In: Encyclopedia of Life Sciences (ELS). Chichester, UK: John Wiley & Sons, Ltd.

Holers VM (2014) Complement and its receptors: new insights into human disease. Annual Review of Immunology 32: 433–459.

Jancar S and Crespo MS (2005) Immune complex‐mediated tissue injury: a multistep paradigm. Trends in Immunology 26: 48–55.

Jennette JC, Falk RJ, Bacon PA, et al. (2012) 2012 Revised international Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis and Rheumatism 65: 1–11.

Karmacharya P, Poudel DR, Pathak R, et al. (2015) Rituximab‐induced serum sickness: a systematic review. Seminars in Arthritis and Rheumatism 45: 334–343.

Kumar V (2010) Diseases of the immune system. In: Kumar V, Abbas AK and Fausto N, 8th edn, Robbins and Cotran Pathologic Mechanisms of Disease, pp. 204–205. Philadelphia, PA: Elsevier.

Nimmerjahn F and Ravetch JV (2008) Fcγ receptors as regulators of immune responses. Nature Reviews Immunology 8: 34–47.

Nobakht E, Cohen CD, Rosenberg AZ, et al. (2016) HIV‐associated immune complex kidney disease. Nature Reviews Nephrology 12: 291–300.

Nydegger UE (2007) Immune complex pathophysiology. Annals of the New York Academy of Sciences 1109: 66–83.

Rich RR (1992) Immune complex diseases. In: Wyngaarden JB, Smith LH Jr and Bennett JC (eds) Cecil's Textbook of Medicine, 19th edn, pp. 1467–1470. Philadelphia, PA: WB Saunders.

Ricklin D and Lambris JD (2013) Complement in immune and inflammatory disorders. Journal of Immunology 190: 3831–3838.

Vermeersch P, Gijbels K, Marien G, et al. (2008) A critical appraisal of current practice in the detection, analysis and reporting of cryoglobulins. Clinical Chemistry 54: 39–43.

Weigle WO and Dixon FJ (1957) The elimination of heterologous serum proteins and associated antibody responses in guinea pigs and rats. The Journal of Immunology 79: 24–33.

Wilson PC and Andrews SF (2012) Tools to therapeutically harness the human antibody response. Nature Reviews Immunology 12: 709–719.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Warren, Jeffrey S, and Ward, Peter A(Apr 2017) Immune Complex Diseases. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002164.pub3]