Abstract
BAFF, APRIL y BAFFR: DIFFERENTIAL BIOMARKERS BETWEEN IgA VASCULITIS AND IgA NEPHROPATHY?
Full text
Background: IgA vasculitis (IgAV) and IgA nephropathy (IgAN) are inflammatory conditions [1, 2], that share pathogenic mechanisms [1], in which B-lymphocytes are described as key cells implicated in these processes. BAFF, APRIL and BAFF-R are cytokines implicated in the development of B-lymphocytes [3, 4] and in autoimmune processes [5, 6]. In this regard, an influence of
BAFF, APRIL
and
BAFFR
polymorphisms was observed on several immune-mediated conditions, being
BAFF
GCTGT>A a shared insertion-deletion variant for inflammatory conditions [7, 8].
Objectives: To determine whether
BAFF, APRIL
and
BAFFR
could be used as differential biomarkers between IgAV and IgAN.
Methods:
BAFF
rs374039502 (which colocalizes with
BAFF
GCTGT>A), two tag variants within
APRIL
(rs11552708 and rs6608) and two tag variants within
BAFFR
(rs7290134 and rs77874543) were genotyped in 394 Caucasian IgAV patients, 95 patients with IgAN and 832 matched healthy controls.
Results: Similar genotype and allele frequencies were observed in the whole cohort of patients with IgAV when compared to those with IgAN when
BAFF, APRIL
and
BAFFR
variants were analyzed independently (
Table 1
). In accordance with that, no
BAFF, APRIL
and
BAFFR
genotype or allele differences were detected between IgAV patients who developed nephritis and patients with IgAN (
Table 1
). Additionally, no statistically significant differences were observed between the whole cohort of patients with IgAV and healthy controls as well as between patients with IgAN and healthy controls when each when
BAFF, APRIL
and
BAFFR
genetic variant was also analyzed independently (
Table 1
). Similar results were disclosed when haplotype frequencies of
APRIL
and
BAFFR
were compared between the different comparative groups above mentioned (data not shown).
Table 1.
Genotype and allele frequencies of BAFF, APRIL and BAFFR in the whole cohort of patients with IgAV, patients with IgAV who developed nephritis, patients with IgAN and healthy controls.
Polymorphism
Change
Data set
Genotypes, % (n)
Alleles, % (n)
1/2
1/1
1/2
2/2
1
2
BAFF
rs374039502
T/A
IgAV
92.1 (363)
7.9 (31)
0.0
96.1 (757)
3.9 (31)
IgAV with nephritis
90.1 (128)
9.9 (14)
0.0
95.1 (270)
4.9 (14)
IgAN
91.6 (87)
8.4 (8)
0.0
95.8 (182)
4.2 (8)
Controls
91.8 (764)
7.8 (65)
0.4 (3)
95.7 (1593)
4.3 (71)
APRIL
rs11552708
G/A
IgAV
78.7 (310)
20.1 (79)
1.3 (5)
88.7 (699)
11.3 (89)
IgAV with nephritis
81.1 (116)
18.9 (27)
0.0
90.6 (259)
9.4 (27)
IgAN
75.8 (72)
23.2 (22)
1.1 (1)
87.4 (166)
12.6 (24)
Controls
78.7 (655)
19.7 (164)
1.6 (13)
88.6 (1474)
11.4 (190)
APRIL
rs6608
C/T
IgAV
72.6 (286)
25.4 (100)
2.0 (8)
85.3 (672)
14.7 (116)
IgAV with nephritis
75.5 (108)
23.1 (33)
1.4 (2)
87.1 (249)
12.9 (37)
IgAN
65.3 (62)
30.5 (29)
4.2 (4)
80.5 (153)
19.5 (37)
Controls
71.0 (591)
26.6 (221)
2.4 (20)
84.3 (1403)
15.7 (261)
BAFFR
rs7290134
A/G
IgAV
58.9 (232)
35.5 (140)
5.6 (22)
76.6 (604)
23.4 (184)
IgAV with nephritis
60.1 (86)
32.2 (46)
7.7 (11)
76.2 (218)
23.8 (68)
IgAN
57.9 (55)
38.9 (37)
3.2 (3)
77.4 (147)
22.6 (43)
Controls
58.7 (488)
35.1 (292)
6.3 (52)
76.2 (1268)
23.8 (396)
BAFFR
rs77874543
G/C
IgAV
83.2 (328)
15.5 (61)
1.3 (5)
91.0 (717)
9.0 (71)
IgAV with nephritis
83.1 (118)
16.9 (24)
0.0
91.5 (260)
8.5 (24)
IgAN
86.3 (82)
13.7 (13)
0.0
93.2 (167)
6.8 (13)
Controls
83.7 (696)
16.0 (133)
0.4 (3)
91.6 (1525)
8.4 (139)
IgAV: IgA vasculitis; IgAN: IgA nephropathy.
Conclusion: Our results reveal a similar
BAFF, APRIL
and
BAFFR
genetic distribution in IgAV and IgAN, suggesting that these genes could not be used as differential biomarkers between these pathologies.
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[1]
N Engl J Med 2013;368:2402-14
;
[2]
Am J Kidney Dis 1988;12:373-7;
[3]
J Exp Med 1999;189:1747-56
;
[4]
Nat Genet 2005;37:793-4;
[5]
Arthritis Res Ther 2018;20:158
;
[6]
Arthritis Res Ther 2020;22:157;
[7]
Engl J Med 2017;376:1615-26
;
[8]
Sci Rep 2018;8:8195
.
Acknowledgements: This study was supported by the European Regional Development Fund (ERDF) and “Fondo de Investigaciones Sanitarias” (grant PI18/00042 and PI21/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) [grant number CM20/00006]; SR-M is supported by funds of the RETICS Program co-funded by ERDF [grant number RD16/0012/0009]; VP-C is supported by a pre-doctoral grant from IDIVAL [grant number PREVAL 18/01]; RL-M is a recipient of a Miguel Servet type II programme fellowship from the ISCIII, co-funded by ESF `Investing in your future´ [grant number CPII21/00004].
Disclosure of Interests: Diana Prieto-Peña: None declared, Fernanda Genre: None declared, Sara Remuzgo Martinez: None declared, Verónica Pulito-Cueto: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda Fillloy: None declared, J. Narváez: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Antonio Fernandez-Nebro: None declared, Gisela Díaz-Cordoves: None declared, Secundino Cigarrán: None declared, Jesús Calviño: None declared, Carmen Cobelo: None declared, Diego de Argila: None declared, Esther F. Vicente-Rabaneda: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galíndez-Agirregoikoa: None declared, Oreste Gualillo: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Miguel A González-Gay Speakers bureau: Abbvie, MSD, Jansen, and Roche, Grant/research support from: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Raquel López-Mejías: None declared
Citation: , volume 81, supplement 1, year 2022, page 1203Session: Vasculitis - aetiology, pathogenesis and animal models
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