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Elevated serum IgG4 defines specific clinical phenotype of rheumatoid arthritis.

Chen LF, Mo YQ, Ma JD, Luo L, Zheng DH, Dai L - Mediators Inflamm. (2014)

Bottom Line: Among 45 patients who received methotrexate and leflunomide therapy, 50% (9/18) of patients with elevated sIgG4 and 85% (23/27) of patients with normal sIgG4 reached therapeutic target (disease activity score of 28 joints < 3.2) at 6-month visit (χ(2) = 6.508, P = 0.011).IgG4-positive plasma cell count correlated positively with sIgG4, total synovitis score, and CD3-, CD20-, and CD38-positive cell counts (all P < 0.05).Our results showed that elevated sIgG4 in RA is common and disproportional to total IgG and RA with elevated sIgG4 may be a specific clinical phenotype with higher disease activity, higher level of autoantibodies, and poor response to methotrexate and leflunomide therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou 510120, China.

ABSTRACT

Objectives: To explore the correlation of serum IgG4 (sIgG4) with clinical manifestations or therapeutic response in rheumatoid arthritis (RA).

Methods: Consecutive 136 RA patients were recruited and followed up at regular interval. SIgG4 was detected by immunonephelometry. Serial synovial tissue sections from 46 RA patients were stained immunohistochemically for IgG4.

Results: Forty-six percent of 136 RA patients had elevated sIgG4. Patients with elevated sIgG4 had higher sIgG4/sIgG ratio, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and anticyclic citrullinated peptide antibodies than those with normal sIgG4 (all P < 0.05). Among 45 patients who received methotrexate and leflunomide therapy, 50% (9/18) of patients with elevated sIgG4 and 85% (23/27) of patients with normal sIgG4 reached therapeutic target (disease activity score of 28 joints < 3.2) at 6-month visit (χ(2) = 6.508, P = 0.011). IgG4-positive plasma cell count correlated positively with sIgG4, total synovitis score, and CD3-, CD20-, and CD38-positive cell counts (all P < 0.05).

Conclusions: Our results showed that elevated sIgG4 in RA is common and disproportional to total IgG and RA with elevated sIgG4 may be a specific clinical phenotype with higher disease activity, higher level of autoantibodies, and poor response to methotrexate and leflunomide therapy.

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Related in: MedlinePlus

Correlation of IgG4-positive plasma cells with serum IgG4 and inflammatory infiltration in synovium of 46 RA patients. Spearman's rank order correlation test showed significant correlation of IgG4-positive plasma cells with serum IgG4 (a), CD3+ (c), CD20+ (d), and CD38+ cells (e). Patients with severe inflammatory infiltration (n = 31) had higher IgG4-positive plasma cells than those with mild inflammatory infiltration in synovium (n = 15) (b).
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fig3: Correlation of IgG4-positive plasma cells with serum IgG4 and inflammatory infiltration in synovium of 46 RA patients. Spearman's rank order correlation test showed significant correlation of IgG4-positive plasma cells with serum IgG4 (a), CD3+ (c), CD20+ (d), and CD38+ cells (e). Patients with severe inflammatory infiltration (n = 31) had higher IgG4-positive plasma cells than those with mild inflammatory infiltration in synovium (n = 15) (b).

Mentions: Spearman's rank order correlation test showed synovial IgG4-positive plasma cells correlated positively and significantly with total synovitis score (r = 0.374, P = 0.010), inflammatory infiltration subscore (r = 0.335, P = 0.023), and density of resident cells subscore (r = 0.364, P = 0.013). Patients were divided into severe inflammatory group (inflammatory infiltration subscore: 2~3, n = 31) and mild inflammatory group (0~1, n = 15). Patients in severe inflammatory group had higher IgG4-positive plasma cells than those in mild inflammatory group (202 ± 189/mm2 versus 49 ± 55/mm2, Figure 3(b)). Positive and significant correlation was found between IgG4-positive plasma cells and CD3-positive (Figure 3(c)), CD20-positive (Figure 3(d)), or CD38-positive cell counts (Figure 3(e)), but not CD68-positive cell count or CD34-positive vessel count (both P > 0.05).


Elevated serum IgG4 defines specific clinical phenotype of rheumatoid arthritis.

Chen LF, Mo YQ, Ma JD, Luo L, Zheng DH, Dai L - Mediators Inflamm. (2014)

Correlation of IgG4-positive plasma cells with serum IgG4 and inflammatory infiltration in synovium of 46 RA patients. Spearman's rank order correlation test showed significant correlation of IgG4-positive plasma cells with serum IgG4 (a), CD3+ (c), CD20+ (d), and CD38+ cells (e). Patients with severe inflammatory infiltration (n = 31) had higher IgG4-positive plasma cells than those with mild inflammatory infiltration in synovium (n = 15) (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4273547&req=5

fig3: Correlation of IgG4-positive plasma cells with serum IgG4 and inflammatory infiltration in synovium of 46 RA patients. Spearman's rank order correlation test showed significant correlation of IgG4-positive plasma cells with serum IgG4 (a), CD3+ (c), CD20+ (d), and CD38+ cells (e). Patients with severe inflammatory infiltration (n = 31) had higher IgG4-positive plasma cells than those with mild inflammatory infiltration in synovium (n = 15) (b).
Mentions: Spearman's rank order correlation test showed synovial IgG4-positive plasma cells correlated positively and significantly with total synovitis score (r = 0.374, P = 0.010), inflammatory infiltration subscore (r = 0.335, P = 0.023), and density of resident cells subscore (r = 0.364, P = 0.013). Patients were divided into severe inflammatory group (inflammatory infiltration subscore: 2~3, n = 31) and mild inflammatory group (0~1, n = 15). Patients in severe inflammatory group had higher IgG4-positive plasma cells than those in mild inflammatory group (202 ± 189/mm2 versus 49 ± 55/mm2, Figure 3(b)). Positive and significant correlation was found between IgG4-positive plasma cells and CD3-positive (Figure 3(c)), CD20-positive (Figure 3(d)), or CD38-positive cell counts (Figure 3(e)), but not CD68-positive cell count or CD34-positive vessel count (both P > 0.05).

Bottom Line: Among 45 patients who received methotrexate and leflunomide therapy, 50% (9/18) of patients with elevated sIgG4 and 85% (23/27) of patients with normal sIgG4 reached therapeutic target (disease activity score of 28 joints < 3.2) at 6-month visit (χ(2) = 6.508, P = 0.011).IgG4-positive plasma cell count correlated positively with sIgG4, total synovitis score, and CD3-, CD20-, and CD38-positive cell counts (all P < 0.05).Our results showed that elevated sIgG4 in RA is common and disproportional to total IgG and RA with elevated sIgG4 may be a specific clinical phenotype with higher disease activity, higher level of autoantibodies, and poor response to methotrexate and leflunomide therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yan Jiang West Road, Guangzhou 510120, China.

ABSTRACT

Objectives: To explore the correlation of serum IgG4 (sIgG4) with clinical manifestations or therapeutic response in rheumatoid arthritis (RA).

Methods: Consecutive 136 RA patients were recruited and followed up at regular interval. SIgG4 was detected by immunonephelometry. Serial synovial tissue sections from 46 RA patients were stained immunohistochemically for IgG4.

Results: Forty-six percent of 136 RA patients had elevated sIgG4. Patients with elevated sIgG4 had higher sIgG4/sIgG ratio, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and anticyclic citrullinated peptide antibodies than those with normal sIgG4 (all P < 0.05). Among 45 patients who received methotrexate and leflunomide therapy, 50% (9/18) of patients with elevated sIgG4 and 85% (23/27) of patients with normal sIgG4 reached therapeutic target (disease activity score of 28 joints < 3.2) at 6-month visit (χ(2) = 6.508, P = 0.011). IgG4-positive plasma cell count correlated positively with sIgG4, total synovitis score, and CD3-, CD20-, and CD38-positive cell counts (all P < 0.05).

Conclusions: Our results showed that elevated sIgG4 in RA is common and disproportional to total IgG and RA with elevated sIgG4 may be a specific clinical phenotype with higher disease activity, higher level of autoantibodies, and poor response to methotrexate and leflunomide therapy.

Show MeSH
Related in: MedlinePlus