Alopecia areata (AA) is an autoimmune disorder in which immune attack of the anagen follicle causes hair loss in approximately 2% of the population. Although the pathogenesis of AA has not been fully determined, most likely it is mediated by a variety of factors including cellular/humoral immunity and genetic predisposition. Researchers have been interested in the possible role of the complement pathway in AA since the 1970s. Given recent evidence suggesting that complement plays a role in many immunologic and inflammatory dermatologic diseases including systemic lupus erythematosus, bullous diseases, angioedema, lipodystrophy, and skin infections, it is likely that complement also contributes to AA pathogenesis. Although early serum studies and immunohistochemical staining have been unimpressive, recent genetics studies may provide evidence that complement does indeed contribute to AA. By determining if complement plays a role in AA, options for novel targeted treatments will become available for those patients with refractory disease.

1.
Holers VM: Complement and its receptors: new insights into human disease. Ann Rev Immunol 2014; 32: 433–459.
2.
Nunzi E, Hamerlinck F, Cormane RH: Immunopathological studies on alopecia areata. Arch Dermatol Res 1980; 269: 1–11.
3.
Lowy M, Ledoux-Corbusier M, Achten G, Wybran J: Clinical and immunologic response to isoprinosine in alopecia areata and alopecia universalis: association with autoantibodies. J Am Acad Dermatol 1985; 12: 78–84.
4.
Dainichi T, Kabashima K: Alopecia areata: What’s new in epidemiology, pathogenesis, diagnosis, and therapeutic options? J Dermatol Sci 2017; 86: 3–12.
5.
Panelius J, Meri S: Complement system in dermatological diseases – fire under the skin. Fronti Med 2015; 2: 3.
6.
Elbendary A, et al: Specificity of granular IgM deposition in folliculosebaceous units and sweat gland apparatus in direct immunofluorescence (DIF) of lupus erythematosus. J Am Acad Dermatol 2016; 75: 404–409:
7.
Alexandru A, et al: Direct immunofluorescence on hair follicles–present and future perspectives. Am J Dermatopathol 2013; 35: 472–476.
8.
Abreu-Velez AM, Klein AD, Howard M: Survivin, p53, MAC, Complement/C3, fibrinogen and HLA-ABC within hair follicles in central and centrifugal cicatricial alopecia. N Am J Med Sci 2011; 3: 292–295.
9.
Poblet E, Jimenez F, Pascual A, Pique E: Frontal fibrosing alopecia versus lichen planopilaris: a clinicopathological study. Int J Dermatol 2006; 45: 375–380.
10.
Berrens L, Jankowski E, Jankowski-Berntsen I: Complement component profiles in urticaria, dermatitis herpetiformis, and alopecia areata. Br J Dermatol 1976; 95: 145–152.
11.
Wuthrich B, Grob PJ, Zisiadis S: Immunological study of alopecia areata (in German). Hautarzt 1980; 31: 495–501.
12.
Herzer P, Czarnetzki BM, Holzmann H, Lemmel EM: Immunological studies in patients with alopecia areata. Int Arch Allergy Appl Immunol 1979; 58: 212–218.
13.
Gilhar A, Pillar T, Assay B, David M: Failure of passive transfer of serum from patients with alopecia areata and alopecia universalis to inhibit hair growth in transplants of human scalp skin grafted on to nude mice. Br J Dermatol 1992; 126: 166–171.
14.
Abdel-Naser MB, Blume-Peytavi U, Abdel-Fatah A, Orfanos CE: Evidence for a complement-mediated inhibition and an antibody-dependent cellular cytotoxicity of dermal fibroblasts in alopecia areata. Acta Derm Venereol 1994; 74: 351–354.
15.
Igarashi R, Takeuchi S, Sato Y: Immunofluorescent studies of complement C3 in the hair follicles of normal scalp and of scalp affected by alopecia areata. Acta Derm Venereol 1980; 60: 33–37.
16.
Igarashi R, Takeuchi S, Sato Y: Deposits of complement C3 in the hair follicle of normal scalp and alopecia areata (in Japanese). Nihon Hifuka Gakkai Zasshi. 1979; 89: 481–483.
17.
Igarashi R, Morohashi M, Takeuchi S, Sato Y: Immunofluorescence studies on complement components in the hair follicles of normal scalp and of scalp affected by alopecia areata. Acta Derm Venereol 1981; 61: 131–135.
18.
Wolf R, Livni E, Feuerman EJ: Immunologic studies in patients with alopecia areata. Arch Dermatol 1981; 117: 455.
19.
Jautova J, Jarcuskova D, Dubivska M, Ficova M: Immunostimulation therapy in patients with alopecia areata (in Slovak). Bratisl Lek Listy 1995; 96: 160–164.
20.
Jautova J, Jarcuskova D, Ficova M, Dubivska M: Alopecia areata – an autoimmune disorder? (in Slovak). Bratisl Lek Listy 1995; 96: 144–147.
21.
Johansson E, Ranki A, Reunala T, Kianto U, Niemi KM: Immunohistological evaluation of alopecia areata treated with squaric acid dibutylester (SADBE). Acta Derm Venereol 1986; 66: 485–490.
22.
Oelert T, Gilhar A, Paus R: T-cell “induced-self” MHC class I/peptide complexes may enable “de novo” tolerance induction to neo-antigens occurring outside of the thymus: lessons from the hair follicle. Exp Dermatol 2017; 26: 529–531.
23.
Redler S, Brockschmidt FF, Forstbauer FF, et al: The TRAF1/C5 locus confers risk for familial and severe alopecia areata. Br J Dermatol 2010; 162: 866–869.
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