Immunological features of patients affected by Barraquer-Simons syndrome.
Acquired partial lipodystrophy
Autoimmunity
Barraquer-Simons syndrome
C3 nephritic factor
Complement system
Lipodystrophy
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
10 01 2020
10 01 2020
Historique:
received:
12
09
2019
accepted:
29
12
2019
entrez:
12
1
2020
pubmed:
12
1
2020
medline:
2
2
2021
Statut:
epublish
Résumé
C3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features among most patients affected by Barraquer-Simons syndrome (BSS), an acquired form of partial lipodystrophy. Moreover, BSS is frequently associated with autoimmune diseases. However, the relationship between complement system dysregulation and BSS remains to be fully elucidated. The aim of this study was to provide a comprehensive immunological analysis of the complement system status, autoantibody signatures and HLA profile in BSS. Thirteen subjects with BSS were recruited for the study. The circulating levels of complement components, C3, C4, Factor B (FB) and Properdin (P), as well as an extended autoantibody profile including autoantibodies targeting complement components and regulators were assessed in serum. Additionally, HLA genotyping was carried out using DNA extracted from peripheral blood mononuclear cells. C3, C4 and FB levels were significantly reduced in patients with BSS as compared with healthy subjects. C3NeF was the most frequently found autoantibody (69.2% of cases), followed by anti-C3 (38.5%), and anti-P and anti-FB (30.8% each). Clinical data showed high prevalence of autoimmune diseases (38.5%), the majority of patients (61.5%) being positive for at least one of the autoantibodies tested. The HLA allele DRB1*11 was present in 54% of BSS patients, and the majority of them (31%) were positive for *11:03 (vs 1.3% in the general population). Our results confirmed the association between BSS, autoimmunity and C3 hypocomplementemia. Moreover, the finding of autoantibodies targeting complement system proteins points to complement dysregulation as a central pathological event in the development of BSS.
Sections du résumé
BACKGROUND
C3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features among most patients affected by Barraquer-Simons syndrome (BSS), an acquired form of partial lipodystrophy. Moreover, BSS is frequently associated with autoimmune diseases. However, the relationship between complement system dysregulation and BSS remains to be fully elucidated. The aim of this study was to provide a comprehensive immunological analysis of the complement system status, autoantibody signatures and HLA profile in BSS. Thirteen subjects with BSS were recruited for the study. The circulating levels of complement components, C3, C4, Factor B (FB) and Properdin (P), as well as an extended autoantibody profile including autoantibodies targeting complement components and regulators were assessed in serum. Additionally, HLA genotyping was carried out using DNA extracted from peripheral blood mononuclear cells.
RESULTS
C3, C4 and FB levels were significantly reduced in patients with BSS as compared with healthy subjects. C3NeF was the most frequently found autoantibody (69.2% of cases), followed by anti-C3 (38.5%), and anti-P and anti-FB (30.8% each). Clinical data showed high prevalence of autoimmune diseases (38.5%), the majority of patients (61.5%) being positive for at least one of the autoantibodies tested. The HLA allele DRB1*11 was present in 54% of BSS patients, and the majority of them (31%) were positive for *11:03 (vs 1.3% in the general population).
CONCLUSIONS
Our results confirmed the association between BSS, autoimmunity and C3 hypocomplementemia. Moreover, the finding of autoantibodies targeting complement system proteins points to complement dysregulation as a central pathological event in the development of BSS.
Identifiants
pubmed: 31924231
doi: 10.1186/s13023-019-1292-1
pii: 10.1186/s13023-019-1292-1
pmc: PMC6954565
doi:
Substances chimiques
C3 protein, human
0
Complement C3
0
Complement C3 Nephritic Factor
0
Complement C4
0
Properdin
11016-39-0
Complement Factor B
EC 3.4.21.47
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9Commentaires et corrections
Type : ErratumIn
Références
Clin Exp Immunol. 1994 Feb;95(2):316-21
pubmed: 8306508
Arthritis Rheum. 2010 Jun;62(6):1781-91
pubmed: 20191588
Blood. 2009 Nov 5;114(19):4261-71
pubmed: 19745068
J Am Acad Dermatol. 2006 Dec;55(6):947-50
pubmed: 17097389
Mol Immunol. 2012 May;51(1):73-81
pubmed: 22387270
Clin Rev Allergy Immunol. 2008 Feb;34(1):85-102
pubmed: 18270862
Front Immunol. 2019 Jan 29;10:64
pubmed: 30761135
Cells. 2019 Jul 19;8(7):
pubmed: 31331105
Clin Endocrinol (Oxf). 2006 May;64(5):573-9
pubmed: 16649979
Endocr Res. 2019 Feb - May;44(1-2):46-54
pubmed: 30182761
N Engl J Med. 1976 Feb 26;294(9):461-5
pubmed: 1246331
N Engl J Med. 2004 Mar 18;350(12):1220-34
pubmed: 15028826
Mol Immunol. 2009 Feb;46(5):755-60
pubmed: 18954909
Semin Cell Dev Biol. 2019 Jan;85:86-97
pubmed: 29292221
Hum Immunol. 2019 Jul;80(7):429-436
pubmed: 30763600
J Am Soc Nephrol. 2017 May;28(5):1603-1613
pubmed: 28096309
Tissue Antigens. 2010 Mar;75(3):287-8
pubmed: 20047644
J Clin Res Pediatr Endocrinol. 2010;2(1):39-42
pubmed: 21274335
Diabetes. 2010 Jan;59(1):200-9
pubmed: 19833879
Science. 1989 Jun 23;244(4911):1483-7
pubmed: 2734615
Tissue Antigens. 2010 Jan;75(1):82-3
pubmed: 20196823
J Pediatr. 1975 Dec;87(6 Pt 1):912-6
pubmed: 1185393
Platelets. 2005 Aug;16(5):307-11
pubmed: 16011982
Rheumatol Int. 2013 Jun;33(6):1387-95
pubmed: 23325094
Nephrology (Carlton). 2018 Oct;23 Suppl 4:11-15
pubmed: 30298653
Front Immunol. 2018 Nov 20;9:2664
pubmed: 30515158
Endocrinol Metab Clin North Am. 2016 Dec;45(4):783-797
pubmed: 27823605
Tissue Antigens. 2010 Mar;75(3):288-9
pubmed: 20047641
Nephrol Dial Transplant. 2019 Feb 1;34(2):193-199
pubmed: 30124958
J Exp Med. 1993 Jun 1;177(6):1827-31
pubmed: 8496694
Medicine (Baltimore). 2004 Jan;83(1):18-34
pubmed: 14747765
Exp Clin Endocrinol Diabetes. 1998;106(1):79-84
pubmed: 9516065
Kidney Int. 2012 Nov;82(10):1084-92
pubmed: 22854646
Clin Exp Rheumatol. 1994 Sep-Oct;12 Suppl 10:S7-14
pubmed: 7955632
J Biol Chem. 1992 May 5;267(13):9210-3
pubmed: 1374388
BMC Nephrol. 2015 Mar 30;16:40
pubmed: 25886501
J Endocrinol Invest. 2019 Jan;42(1):61-73
pubmed: 29704234
Arthritis Res Ther. 2018 Oct 3;20(1):221
pubmed: 30285828
J Rheumatol. 2005 Aug;32(8):1481-7
pubmed: 16078323
J Allergy Clin Immunol. 2017 Jul;140(1):57-59
pubmed: 28322851
Mol Immunol. 2010 Apr;47(7-8):1476-83
pubmed: 20193965
J Clin Endocrinol Metab. 2016 Dec;101(12):4500-4511
pubmed: 27710244
Case Rep Dermatol. 2015 Apr 25;7(1):70-4
pubmed: 26034476
Clin Exp Immunol. 2016 Apr;184(1):118-25
pubmed: 26660535
Proc Natl Acad Sci U S A. 2015 Dec 29;112(52):15970-5
pubmed: 26598658
J Clin Endocrinol Metab. 2009 Jan;94(1):10-6
pubmed: 18854390
Biochem Biophys Res Commun. 2018 Jan 1;495(1):740-748
pubmed: 29137982
Methods Mol Biol. 2015;1310:231-45
pubmed: 26024639
Autoimmun Rev. 2008 Sep;7(8):621-5
pubmed: 18603025
Lancet. 1974 Jun 22;1(7869):1269-75
pubmed: 4134154
Nat Rev Nephrol. 2019 Mar;15(3):129-143
pubmed: 30692664
J Biol Chem. 2015 Oct 16;290(42):25343-55
pubmed: 26245903
Br J Haematol. 2014 Sep;166(5):729-38
pubmed: 24931452
N Engl J Med. 2011 Dec 15;365(24):2340-2
pubmed: 22168663
Tissue Antigens. 2010 Mar;75(3):286-7
pubmed: 20047642
Br J Haematol. 2002 Dec;119(3):713-5
pubmed: 12437649
J Immunol. 2018 Apr 15;200(8):2786-2797
pubmed: 29531168