3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Kidney Involvement in Hypocomplementemic Urticarial Vasculitis Syndrome—A Case-Based Review

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Hypocomplementemic urticarial vasculitis syndrome (HUVS), or McDuffie syndrome, is a rare small vessel vasculitis associated with urticaria, hypocomplementemia and positivity of anti-C1q antibodies. In rare cases, HUVS can manifest as an immune-complex mediated glomerulonephritis with a membranoproliferative pattern of injury. Due to the rarity of this disorder, little is known about the clinical manifestation, pathogenesis, treatment response and outcome of such patients. We describe here three cases of HUVS with severe renal involvement. These patients had a rapidly progressive form of glomerulonephritis with severe nephrotic syndrome against a background of a membranoproliferative pattern of glomerular injury with extensive crescent formation. Therefore, these patients required aggressive induction and maintenance immunosuppressive therapy, with a clinical and renal response in two patients, while the third patient progressed to end-stage renal disease. Because of the rarity of this condition, there are few data regarding the clinical presentation, pathology and outcome of such patients. Accordingly, we provide an extensive literature review of cases reported from 1976 until 2020 and place them in the context of the current knowledge of HUVS pathogenesis. We identified 60 patients with HUVS and renal involvement that had adequate clinical data reported, out of which 52 patients underwent a percutaneous kidney biopsy. The most frequent renal manifestation was hematuria associated with proteinuria (70% of patients), while one third had abnormal kidney function on presentation (estimated glomerular filtration (GFR) below 60 mL/min/1.73 m 2). The most frequent glomerular pattern of injury was membranoproliferative (35%), followed by mesangioproliferative (21%) and membranous (19%). Similar to other systemic vasculitis, renal involvement carries a poorer prognosis, but the outcome can be improved by aggressive immunosuppressive treatment.

          Related collections

          Most cited references68

          • Record: found
          • Abstract: found
          • Article: not found

          Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies.

          The complement system plays a paradoxical role in the development and expression of autoimmunity in humans. The activation of complement in systemic lupus erythematosus (SLE) contributes to tissue injury. In contrast, inherited deficiency of classical pathway components, particularly C1q (ref. 1), is powerfully associated with the development of SLE. This leads to the hypothesis that a physiological action of the early part of the classical pathway protects against the development of SLE (ref. 2) and implies that C1q may play a key role in this respect. C1q-deficient (C1qa-/-) mice were generated by gene targeting and monitored for eight months. C1qa-/- mice had increased mortality and higher titres of autoantibodies, compared with strain-matched controls. Of the C1qa-/- mice, 25% had glomerulonephritis with immune deposits and multiple apoptotic cell bodies. Among mice without glomerulonephritis, there were significantly greater numbers of glomerular apoptotic bodies in C1q-deficient mice compared with controls. The phenotype associated with C1q deficiency was modified by background genes. These findings are compatible with the hypothesis that C1q deficiency causes autoimmunity by impairment of the clearance of apoptotic cells.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A Hierarchical Role for Classical Pathway Complement Proteins in the Clearance of Apoptotic Cells in Vivo

            The strongest susceptibility genes for the development of systemic lupus erythematosus (SLE) in humans are null mutants of classical pathway complement proteins. There is a hierarchy of disease susceptibility and severity according to the position of the missing protein in the activation pathway, with the severest disease associated with C1q deficiency. Here we demonstrate, using novel in vivo models of apoptotic cell clearance during sterile peritonitis, a similar hierarchical role for classical pathway complement proteins in vivo in the clearance of apoptotic cells by macrophages. Our results constitute the first demonstration of an impairment in the phagocytosis of apoptotic cells by macrophages in vivo in a mammalian system. Apoptotic cells are thought to be a major source of the autoantigens of SLE, and impairment of their removal by complement may explain the link between hereditary complement deficiency and the development of SLE.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              C1q, autoimmunity and apoptosis.

              Deficiency of classical pathway complement components displays a hierarchical association with the development of systemic lupus erythematosus (SLE). Individuals with deficiency of C1q, the first component of the classical pathway of activation, have the highest prevalence of SLE and the most severe manifestations of the disease. However, complement is also implicated in the effector inflammatory phase of the autoimmune response that characterizes SLE. Complement proteins are deposited in inflamed tissues causing consumption of complement. In addition, autoantibodies to C1q develop as part of the autoantibody response. Understanding how C1q deficiency results in the autoimmune phenotype of SLE may provide valuable clues to the role of the complement system in the maintenance of immune tolerance. In this review firstly we discuss the relationship between C1q deficiency and/or consumption and lupus. Secondly, we consider the links between apoptosis and complement. Finally we review the lessons we have learned from a murine model of C1q deficiency discussing the experimental evidence in support of the hypothesis that C1q may critically influence the immune response to self-antigens contained within the surface blebs generated by apoptotic cells.
                Bookmark

                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                06 July 2020
                July 2020
                : 9
                : 7
                : 2131
                Affiliations
                [1 ]Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania; oana.catalina_ion@ 123456yahoo.ro (O.I.); obriscabogdan@ 123456yahoo.com (B.O.); bogdan.sorohan@ 123456yahoo.com (B.S.); sonia.balanica@ 123456gmail.com (S.B.)
                [2 ]Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; gmircescu@ 123456hotmail.com (G.M.); umfisinescu@ 123456gmail.com (I.S.)
                [3 ]“Dr. Carol Davila” Teaching Hospital of Nephrology, 010731 Bucharest, Romania
                [4 ]Center of Uronephrology and Renal Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
                Author notes
                [* ]Correspondence: gener.ismail@ 123456umfcd.ro ; Tel.: +40-722-792-429
                Author information
                https://orcid.org/0000-0003-4796-4950
                https://orcid.org/0000-0003-3574-4635
                Article
                jcm-09-02131
                10.3390/jcm9072131
                7408727
                32640739
                e2f2d0b3-48e0-4603-be2c-345ceffa371a
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 May 2020
                : 03 July 2020
                Categories
                Review

                hypocomplementemic urticarial vasculitis syndrome (huvs),kidney involvement,crescentic glomerulonephritis,nephrotic syndrome,anti-c1q antibodies

                Comments

                Comment on this article