Objective To explore the associations of novel serum autoantibodies with disease activity and organ injuries in patients with lupus nephritis (LN). Method This study included 75 patients with active LN (5 class II, 37 class IV, and 33 class V). Indirect immunofluorescence was used to measure serum anti-dsDNA; ELISA was used to measure serum anti-PLA2R and anti-C1q, and the Luminex method was used to measure 58 novel serum autoantibodies, with a median fluorescence intensity (MFI)/threshold ≥ 1.5 as the antibody positivity cutoff. Results The positivity rates for 11 novel antibodies (anti-PLA2R, anti-P2RY11, anti-DEXI, anti-HARS, anti-TUBA1B, anti-KRT8, anti-TUBB, anti-NCL, anti-HSPB1, anti-AGRN, and anti-LGALS8) were highly associated with SLE activity and were inconsistent with those for anti-dsDNA and anti-C1q. Anti-TUBA1B and anti-AGRN positivity may independently influence LN with extrarenal organ involvement (OR = 6.73, 95% CI = 1.19 ~ 38.09; OR = 6.11, 95% CI = 1.32 ~ 28.25, respectively). The positivity rate for anti-PLA2R as detected by the Luminex platform was 40%, whereas the rate among those detected by ELISA was 12.7%. Twenty-one patients who achieved renal remission were retested, and the positivity rates of anti-PLA2R (42.9% vs. 9.5%, P = 0.014), anti-KRT8 (47.6% vs. 4.8%, P = 0.001), and anti-AGRN (38.1% vs. 4.8%, P = 0.008) also significantly decreased from baseline. Conclusion On the basis of Luminex technology, the present study revealed multiple novel autoantibodies related to SLE activity and organ injury, especially anti-PLA2R, anti-KRT8, and anti-AGRN, thereby providing novel serological markers for the assessment of activity in patients with LN. Anti-TUBA1B and anti-AGRN are strongly associated with extrarenal involvement. <Table Float="No" ID="Taba"> <tgroup cols="1"> <colspec align="left" colname="c1" colnum="1" /> <tbody> <row> <entry align="left" colname="c1"> Key Points </entry> </row> <row> <entry align="left" colname="c1"> • The Luminex method is highly sensitive and high-throughput for detecting serum autoantibodies. • LN patients with anti-TUBA1B and anti-AGRN positivity are more likely to be complicated by extrarenal organ involvement. • Serum anti-PLA2R, anti-KRT8, and anti-AGRN reflect the activity of SLE and provide novel serological markers for the evaluation of LN patients negative for anti-dsDNA and anti-C1q. </entry> </row> </tbody> </tgroup> </Table>

Luminex-based pilot study identifies novel serum autoantibodies associated with disease activity in patients with lupus nephritis

期刊论文
发表日期：

2025年6月11日

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Huan Zhang,
Jiayi Deng,
Yang Liu,
Wen Xia,
Lulu Zhuang,
Houan Zhou,
Zhengzhao Liu,
Haitao Zhang,
Weixin Hu

摘要

Objective

To explore the associations of novel serum autoantibodies with disease activity and organ injuries in patients with lupus nephritis (LN).

Method

This study included 75 patients with active LN (5 class II, 37 class IV, and 33 class V). Indirect immunofluorescence was used to measure serum anti-dsDNA; ELISA was used to measure serum anti-PLA2R and anti-C1q, and the Luminex method was used to measure 58 novel serum autoantibodies, with a median fluorescence intensity (MFI)/threshold ≥ 1.5 as the antibody positivity cutoff.

Results

The positivity rates for 11 novel antibodies (anti-PLA2R, anti-P2RY11, anti-DEXI, anti-HARS, anti-TUBA1B, anti-KRT8, anti-TUBB, anti-NCL, anti-HSPB1, anti-AGRN, and anti-LGALS8) were highly associated with SLE activity and were inconsistent with those for anti-dsDNA and anti-C1q. Anti-TUBA1B and anti-AGRN positivity may independently influence LN with extrarenal organ involvement (OR = 6.73, 95% CI = 1.19 ~ 38.09; OR = 6.11, 95% CI = 1.32 ~ 28.25, respectively). The positivity rate for anti-PLA2R as detected by the Luminex platform was 40%, whereas the rate among those detected by ELISA was 12.7%. Twenty-one patients who achieved renal remission were retested, and the positivity rates of anti-PLA2R (42.9% vs. 9.5%, P = 0.014), anti-KRT8 (47.6% vs. 4.8%, P = 0.001), and anti-AGRN (38.1% vs. 4.8%, P = 0.008) also significantly decreased from baseline.

Conclusion

On the basis of Luminex technology, the present study revealed multiple novel autoantibodies related to SLE activity and organ injury, especially anti-PLA2R, anti-KRT8, and anti-AGRN, thereby providing novel serological markers for the assessment of activity in patients with LN. Anti-TUBA1B and anti-AGRN are strongly associated with extrarenal involvement.

Key Points

• The Luminex method is highly sensitive and high-throughput for detecting serum autoantibodies.

• LN patients with anti-TUBA1B and anti-AGRN positivity are more likely to be complicated by extrarenal organ involvement.

• Serum anti-PLA2R, anti-KRT8, and anti-AGRN reflect the activity of SLE and provide novel serological markers for the evaluation of LN patients negative for anti-dsDNA and anti-C1q.