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      Distal Angiopathy and Atypical Hemolytic Uremic Syndrome: Clinical and Functional Properties of an Anti-Factor H IgAλ Antibody.

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          Abstract

          Abnormal regulation of the alternative pathway of the complement system is a well-described trigger of microangiopathy leading to atypical hemolytic uremic syndrome (aHUS). However, the involvement of complement dysregulation in distal angiopathy has not been reported in adults. We describe the clinical course of a patient with severe distal angiopathy (amputation of all fingers and toes) followed 3 years later by aHUS with end-stage renal disease. This course was attributed to a circulating monoclonal immunoglobulin A λ light chain (IgAλ) with unusual properties: it bound complement factor H (CFH) and impaired CFH-glycosaminoglycan interaction and cell-surface protection. Local complement activation with distal angiopathy and microvascular injury was suggested by deposition of IgA, C4d, and C5b-9 in limb and preglomerular arteries. We therefore postulated that the monoclonal IgAλ inhibited activity of endothelial cell-bound CFH, which led to local activation of complement, vasoconstriction (distal angiopathy), and aHUS. While the patient was dependent on dialysis and plasma exchange, treatment with the anti-C5 antibody eculizumab induced remission of distal angiopathy and aHUS. During eculizumab treatment, kidney transplantation was performed. The patient had normal kidney function at the 3-year follow-up. We suggest that the association of distal angiopathy and aHUS in this patient is clearly linked to anti-CFH properties of the monoclonal IgAλ.

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          Author and article information

          Journal
          Am. J. Kidney Dis.
          American journal of kidney diseases : the official journal of the National Kidney Foundation
          Elsevier BV
          1523-6838
          0272-6386
          Aug 2015
          : 66
          : 2
          Affiliations
          [1 ] Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; INSERM U1026, Université de Bordeaux, Bordeaux, France. Electronic address: claire.rigothier@chu-bordeaux.fr.
          [2 ] Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
          [3 ] Complement and Diseases Team, INSERM UMRS 1138, Cordeliers Research Center, Paris, France; Université Paris Descartes Sorbonne Paris-Cité, Paris, France; Université Pierre et Marie Curie (UPMC-Paris-6), Paris, France.
          [4 ] Laboratoire d'Immunologie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
          [5 ] INSERM U1026, Université de Bordeaux, Bordeaux, France; Laboratoire de Pathologie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
          [6 ] Service de Néphrologie, Hémodialyse et Transplantation Rénale, Centre Hospitalier Universitaire de Poitiers, Poitiers, France; Centre de référence des amyloses primitives et des maladies de dépôts d'immunoglobulines monoclonales, Poitiers, France.
          [7 ] Centre de référence des amyloses primitives et des maladies de dépôts d'immunoglobulines monoclonales, Poitiers, France; Laboratoire d'Anatomie et cytologie Pathologiques, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
          [8 ] Complement and Diseases Team, INSERM UMRS 1138, Cordeliers Research Center, Paris, France; Assistance Publique-Hopitaux de Paris, Service d'Immunologie biologique, Hôpital Européen Georges Pompidou, Paris, France.
          [9 ] Service de Néphrologie Transplantation Dialyse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; INSERM U1026, Université de Bordeaux, Bordeaux, France.
          Article
          S0272-6386(15)00706-4
          10.1053/j.ajkd.2015.03.039
          26015278

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