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Journal of Peking University (Health Sciences) ›› 2025, Vol. 57 ›› Issue (5): 911-918. doi: 10.19723/j.issn.1671-167X.2025.05.015

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Expression of lumican protein in serum of patients with rheumatoid arthritis and its correlation with disease and immune activities

Ju YANG1,2, Jing XU3, Juhua DAI4, Lianjie SHI5,*()   

  1. 1. Department of Geriatrics, Suining Central Hospital, Suining 629000, Sichuan, China
    2. Department of Clinical Medicine, North Sichuan Medical College, Nanchong 637000, Sichuan, China
    3. Department of Rheumatology and Immunology, Peking University International Hospital, Beijing 102206, China
    4. Department of Clinical Laboratory, Peking University International Hospital, Beijing 102206, China
    5. Department of Rheumatology and Immunology, Peking University Shougang Hospital, Beijing 100144, China
  • Received:2023-01-28 Online:2025-10-18 Published:2025-01-06
  • Contact: Lianjie SHI
  • Supported by:
    the Peking University International Hospital Research Funds(YN2020ZD01)

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Abstract: Objective: To investigate the serum level of lumican (LUM) and its clinical correlation with disease and immune activities in patients with rheumatoid arthritis (RA). Methods: The serum LUM levels in both RA patients and health controls (HCs) were detected by enzyme-linked immunosorbent assay (ELISA). The clinical and laboratory data of the patients were collected. The LUM levels in the patients with different clinical features were analyzed. The correlation between the clinical data, laboratory parameters, and serum LUM levels were also analyzed. Independent samples t test, Spearman correlation were used for statistical analysis. Analysis of variance and Kruskal-Wallis test, the least significant difference (LSD)-t test and Bonferroni correction were used for statistical analysis. The Pearson Chi-square test was used for comparison of the rates between the groups. Statistical significance was set at P < 0.05. Results: The levels of LUM were elevated in the RA patients than in the HCs (P < 0.000 1). Serum LUM levels were correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A (IgA), titers of platelet (PLT) and 28-joint disease activity score (DAS28, all P < 0.05). Next, we compared the serum LUM levels in the RA patients with different characteristics, and no difference was found in serum LUM levels between early-RA and RA, the same to RA with different gender (P>0.05). The levels of serum LUM were elevated in the RF positive patients (P < 0.000 1), and in the RF and anti-CCP positive patients (P < 0.05) than in the RA patients with negative RF whether the anti-CCP was positive. In addition, no differences were found between the RA patients with negative RF whether the anti-CCP was positive (P>0.05). All the levels of serum LUM were elevated in the RA patients with different CRP or ESR than in the HCs (P < 0.05), and the serum LUM levels in the RA patients with elevated ESR and CRP were significantly elevated in those with normal ESR and CRP (P < 0.05). Additionally, the results demonstrated that serum LUM levels were positively associated with RA disease activity, and they were declined in RA sustained remission than those in middle or high disease activity (P < 0.05). Furthermore, no difference was found between the RA patients in remission and HCs (P>0.05). No differences were found in the RA patients with and without complications including interstitial pneumonia disease, Sjögren's syndrome, thyroid gland diseases and osteoporosis (P>0.05). The LUM positivity rates were significantly elevated in the RF positive patients than the RF negative patients in RA (P < 0.05). Conclusion: LUM, a cyclocitrullinated protein, might be a promising biomarker which could reflect both disease activity and immune activity in RA.

Key words: Lumican, Rheumatoid arthritis, Rheumatoid factor, Anti-citrullinated protein antibodies

CLC Number: 

  • R593.22

Table 1

General demography, clinical characteristics and serum LUM level in patients with RA"

Characteristics Data
RA (n=133)
  Seropositive 115 (86.5)
  Seronegative 18 (13.5)
Gender (n=133)
  Male 32 (24.1)
  Female 101 (75.9)
  Age/years 58.26±14.31
Laboratory features
  ESR/(mm/h) (n=124) 36.00 (13.25, 73.00)
  CRP/(mg/L) (n=131) 12.52 (2.80, 50.29)
  RF/(IU/mL) (n=133) 86.60 (23.05, 280.00)
  Anti-CCP/(U/mL) (n=126) 234.95 (73.58, 444.73)
  IgA/(g/L) (n=105) 2.83 (1.97, 3.90)
  IgM/(g/L) (n=105) 1.26 (0.91, 1.59)
  IgG/(g/L) (n=105) 13.73 (11.36, 17.00)
  C3/(g/L) (n=104) 1.22±0.31
  C4/(g/L) (n=104) 0.20 (0.16, 0.26)
  PLT/(×109/L) (n=125) 268 (203, 339)
RA activity (score according to DAS28-CRP) (n=133)*
  HDA (n=64) 23.66±5.13
  MDA (n=35) 22.37±5.13
  LDA (n=8) 21.92±6.15
  Remission (n=20) 18.88±5.19
Complications (n=133)
  ILD 16 (12.0)
  SS 10 (7.5)
  TGD 38 (28.6)
  OP 50 (37.6)
LUM/(μg/L) (n=133) 22.17±5.47

Figure 1

Serum LUM levels in patients with RA (n=133) and HCs (n=64) HCs, healthy controls; RA, rheumatoid arthritis; LUM, lumican."

Table 2

Correlation between serum LUM level and clinical characteristics in patients with RA"

Characteristics Serum LUM levels
R P
Age 0.132 0.130
Disease duration 0.032 0.715
ESR 0.295 0.001**
CRP 0.229 0.008**
RF 0.366 ＜0.001***
Anti-CCP 0.129 0.150
IgA 0.227 0.020**
IgM 0.163 0.097
IgG 0.170 0.082
C3 0.128 0.195
C4 -0.147 0.136
PLT 0.299 0.001**
DAS28-CRP 0.274 0.002**

Figure 2

Serum LUM levels in RA patients with different clinical and laboratory characteristics *P < 0.05, **P < 0.01, ***P < 0.001. A, serum LUM levels in RA patients with different disease durations (early RA: ≤ 2 years; RA: > 2 years); B, serum LUM levels in RA patients with different sexes; C, serum LUM levels in RA patients with different levels of RF and anti-CCP; D, serum LUM levels in RA patients with different levels of CRP and ESR; E, RA patients with different disease activity (Remission: DAS28 ≤ 2.6; LDA: 2.6 < DAS28 ≤ 3.2; MDA: 3.2 < DAS28 ≤ 5.1; HDA: DAS28 > 5.1). HCs, healthy controls; NS, no significant; Other abbreviations as in Table 1."

Figure 3

Serum LUM levels in RA patients with or without different complications or comorbidities A, RA patients with or without interstitial lung disease (ILD); B, RA patients with or without Sjögren syndrome (SS); C, RA patients with or without thyroid gland diseases (TGD); D, RA patients with or without osteoporosis (OP). RA, rheumatoid arthritis; LUM, lumican."

Table 3

The positive rate of LUM in RA patients with different levels of serum RF or anti-CCP"

Group RA with LUM, n (%) RA without LUM, n (%) χ2 value P value
RF+ 63 (60.0) 42 (40.0) 8.774 0.003
RF- 8 (28.6) 20 (71.4)
Anti-CCP+ 64 (59.8) 43 (40.2) 3.461 0.063
Anti-CCP- 7 (36.8) 12 (63.2)
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