TY - JOUR
T1 - B-cell activating factor and IL-21 levels predict treatment response in autoimmune hepatitis
AU - Biewenga, Maaike
AU - Heidt, Sebastiaan
AU - Vergunst, Manon
AU - Marijnissen, Camiel M.J.
AU - de Man, Rob A.
AU - van der Eijk, Annemiek A.
AU - van der Meer, Adriaan J.
AU - Trouw, Leendert A.
AU - van Hoek, Bart
N1 - Funding Information:
MB was supported by unrestricted grants from Zambon Pharma, the Netherlands .
Publisher Copyright:
© 2022 The Authors
PY - 2022/5
Y1 - 2022/5
N2 - Background & Aims: Increased serum IgG and autoantibodies suggest involvement of B cells in autoimmune hepatitis (AIH). The aim of this study was to assess levels of B cell activating factor of the tumour necrosis family (BAFF), IL-21, and circulating B cell populations in AIH and correlate these to treatment response. Methods: BAFF and IL-21 levels were determined in 66 patients with AIH before treatment and 10 healthy controls. Flow cytometry was performed on circulating B cells of 10 patients with AIH and 12 healthy controls. Results: Based on BAFF and IL-21 levels, untreated patients with AIH were divided into 3 groups: 27 (41%) patients with normal BAFF and IL-21 (normal BAFF), 27 (41%) patients with elevated BAFF but normal IL-21 (high BAFF), and 12 (18%) patients with elevated IL-21 (high IL-21). The high BAFF group presented with higher bilirubin compared with the normal BAFF and high IL-21 groups (159 vs. 26 vs. 89 μmol/L; p = 0.001; Mann–Whitney U test). After 12 months of treatment, 54% of the high BAFF group reached remission compared with 34% of the normal BAFF group and 0% of the high IL-21 group (p = 0.006, Chi-square test). During follow-up, 3 patients (25%) with high IL-21 developed primary sclerosing cholangitis (PSC) variant syndrome. Autoimmune-associated B cells were increased in patients with AIH compared with healthy controls (4.4 vs. 1.4%; p = 0.003, Mann–Whitney U test). BAFF levels were correlated positively with naïve B cells (p = 0.01) and negatively with class-switched B cells (p = 0.003) and nonclass-switched B cells (p = 0.005, Spearman correlation). Discussion: Using BAFF and IL-21, we identified different immunological phenotypes of AIH with a different presentation, treatment response, and outcome. Patients with high IL-21 had the poorest treatment response and a risk of developing PSC variant syndrome. BAFF level was related to shifts in circulating B-cell populations. Lay summary: In patients with untreated autoimmune hepatitis (AIH), circulating B-cell activating factor of the tumour necrosis family (BAFF), IL-21, and B-cell populations were determined. Three subgroups were identified: with (1) normal BAFF and IL-21, (2) elevated BAFF and normal IL-21, and (3) elevated IL-21. Remission after 1-year treatment occurred in 54, 34, and 0% in Groups 1, 2, and 3, respectively. Group 2 had higher bilirubin, indicating more liver dysfunction. In 25% of patients with high IL-21, AIH-PSC variant syndrome developed, but none in the other groups. Autoimmune-associated B cells were elevated and BAFF levels correlated with certain B cells.
AB - Background & Aims: Increased serum IgG and autoantibodies suggest involvement of B cells in autoimmune hepatitis (AIH). The aim of this study was to assess levels of B cell activating factor of the tumour necrosis family (BAFF), IL-21, and circulating B cell populations in AIH and correlate these to treatment response. Methods: BAFF and IL-21 levels were determined in 66 patients with AIH before treatment and 10 healthy controls. Flow cytometry was performed on circulating B cells of 10 patients with AIH and 12 healthy controls. Results: Based on BAFF and IL-21 levels, untreated patients with AIH were divided into 3 groups: 27 (41%) patients with normal BAFF and IL-21 (normal BAFF), 27 (41%) patients with elevated BAFF but normal IL-21 (high BAFF), and 12 (18%) patients with elevated IL-21 (high IL-21). The high BAFF group presented with higher bilirubin compared with the normal BAFF and high IL-21 groups (159 vs. 26 vs. 89 μmol/L; p = 0.001; Mann–Whitney U test). After 12 months of treatment, 54% of the high BAFF group reached remission compared with 34% of the normal BAFF group and 0% of the high IL-21 group (p = 0.006, Chi-square test). During follow-up, 3 patients (25%) with high IL-21 developed primary sclerosing cholangitis (PSC) variant syndrome. Autoimmune-associated B cells were increased in patients with AIH compared with healthy controls (4.4 vs. 1.4%; p = 0.003, Mann–Whitney U test). BAFF levels were correlated positively with naïve B cells (p = 0.01) and negatively with class-switched B cells (p = 0.003) and nonclass-switched B cells (p = 0.005, Spearman correlation). Discussion: Using BAFF and IL-21, we identified different immunological phenotypes of AIH with a different presentation, treatment response, and outcome. Patients with high IL-21 had the poorest treatment response and a risk of developing PSC variant syndrome. BAFF level was related to shifts in circulating B-cell populations. Lay summary: In patients with untreated autoimmune hepatitis (AIH), circulating B-cell activating factor of the tumour necrosis family (BAFF), IL-21, and B-cell populations were determined. Three subgroups were identified: with (1) normal BAFF and IL-21, (2) elevated BAFF and normal IL-21, and (3) elevated IL-21. Remission after 1-year treatment occurred in 54, 34, and 0% in Groups 1, 2, and 3, respectively. Group 2 had higher bilirubin, indicating more liver dysfunction. In 25% of patients with high IL-21, AIH-PSC variant syndrome developed, but none in the other groups. Autoimmune-associated B cells were elevated and BAFF levels correlated with certain B cells.
UR - http://www.scopus.com/inward/record.url?scp=85127127201&partnerID=8YFLogxK
U2 - 10.1016/j.jhepr.2022.100460
DO - 10.1016/j.jhepr.2022.100460
M3 - Article
C2 - 35368991
AN - SCOPUS:85127127201
SN - 2589-5559
VL - 4
JO - JHEP Reports
JF - JHEP Reports
IS - 5
M1 - 100460
ER -