Diagnostic value of a novel salivary gland ultrasound scoring system in IgG4-related sialadenitis.

OBJECTIVES: To develop a novel ultrasound scoring system for the major salivary glands in patients with immunoglobulin G4-related sialadenitis (IgG4-RS) and assess its diagnostic value in a multicenter cohort of Chinese patients. METHODS: Twenty clinicians (rheumatologists, stomatologists, and radiologists) participated. The study was conducted in four steps: (1) defining the ultrasonography (US) elements, (2) developing a novel ultrasound scoring system for US of the salivary glands, (3) evaluation of inter- and intra-reader reliabilities using the new ultrasound scoring system, and (4) assessing the diagnostic value of this novel ultrasound scoring system in IgG4-RS patients in a Chinese multicenter cohort. RESULTS: A novel ultrasound scoring system for the salivary glands was developed, with total scores ranging from 0 to 34. The inter- and intra-reader reliabilities of the ultrasound scoring system were excellent (0.972 and 0.940, respectively). A total of 470 people were recruited in this study; 187 patients were diagnosed with IgG4-RS, and the remaining 283 people were diagnosed with non-IgG4-RS. Patients with IgG4-RS had significantly higher US scores than the non-IgG4-RS group (mean US score=16 vs. 4, P < 0.001). The calculated area under the curve (AUC) for the total US score was 0.852 (95% CI: 0.814-0.891). The total US scores≥9 showed a sensitivity of 75.4% and a specificity of 91.9%. Association analysis showed a positive correlation between total US scores and serum IgG4 levels and hypocomplementemia (r=0.221, r=0.349; P = 0.002) and a negative correlation between total US scores and serum C3 and C4 levels (r=-0.210, r=-0.303; P = 0.005, P < 0.001). CONCLUSIONS: A novel semiquantitative ultrasound scoring system for patients with IgG4-RS was developed, with good diagnostic performance. The inter- and intra-reader reliabilities were excellent. US scores were correlated with IgG4, C3, and C4 levels and hypocomplementemia.

Decreased natural killer T-like cells correlated to disease activity in systemic lupus erythematosus.

OBJECTIVES: To evaluate the absolute numbers and frequencies of natural killer T-like (NKT-like) cells in systemic lupus erythematosus (SLE) and to characterize the possible role of the cells. METHODS: Seventy-nine patients with SLE together with 30 age- and sex-matched healthy controls were enrolled. Flow cytometric determination of peripheral NKT-like cells was carried out for all participants by detecting the absolute counts (Abs) and percentage (%) of CD3 + CD16 + CD56 + cells. Disease activity index, laboratory parameters, and clinical manifestations were collected. The correlation between the cells and these parameters was analyzed. RESULTS: SLE patients had, with respect to controls, considerably decreased values of NKT-like cells (P < 0.001 in both absolute number and percentage). The absolute number of NKT-like cells was found to have positive correlations with WBC, RBC, PLT, C3, C4, IgM and negative correlations with the disease duration, SLEDAI-2 K, anti-dsDNA, anti-nucleosome, anti-ribosomal protein, CRP, ESR. Meanwhile, it was found that the percentage values of NKT-like cells decreased in SLE patients with nephritis which was correlated with anti-ribosomal protein and CRP in comparison to SLE patients without nephritis. Moreover, an increase in the NKT-like cell counts was also observed in the patients with a clinical response to the treatment. CONCLUSIONS: The absolute counts and frequencies of NKT-like cells decreased in SLE patients significantly, which correlated to disease activities and could recover to normal after the treatment. The NKT-like cells may play an important role in the pathogenesis of SLE and could be a useful marker in the disease assessment. Key Points • The absolute counts and frequencies of NKT-like cells decreased in SLE patients significantly. • NKT-like cells were related to the disease activities and could restore after the treatment. • NKT-like cells may be a useful marker in the disease assessment.

Salivary gland ultrasonography in primary Sjögren's syndrome from diagnosis to clinical stratification: a multicentre study.

BACKGROUND: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjögren's syndrome (pSS) using the novel Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system in a large-scale multicentre study. METHODS: SGUS was conducted for 246 pSS patients, 140 control subjects with conditions other than SS and 27 healthy control subjects. The echostructure features from the parotid and submandibular glands on both sides were graded using the novel OMERACT scoring system. Receiver operating characteristic curves were used to describe the diagnostic accuracy of the scoring system for pSS. The associations between the SGUS and disease characteristics were analysed to evaluate the clinical value of SGUS for pSS. RESULTS: The US scores in the pSS group were significantly higher than those in the non-pSS group (p < 0.001). The level of diagnostic accuracy was comparable with the scores of all four glands (AUC=0.908) when only the parotid and submandibular glands on either side were scored (AUC=0.910, 0.904, respectively). The optimal cut-off value for the left (right) parotid gland and the left (right) submandibular gland was 4, with maximal sensitivity (75.6% and 77.2%, respectively) and specificity (91.6% and 92.2%, respectively). The pSS patients with positive SGUS results presented a longer disease duration, parotid enlargement, dental loss and higher levels of serological markers, such as anti-SSA, anti-SSB, positive RF, IgG and γ-globulin%. CONCLUSIONS: SGUS with the OMERACT scoring system yields high sensitivity and specificity, demonstrating high diagnostic feasibility for pSS. The SGUS may have implications for deciding disease severity and treatment efficacy.

Sonoelastography of salivary glands for diagnosis and clinical evaluation in primary Sjögren's syndrome.

OBJECTIVES: To explore the performance of sonoelastography (SE) in diagnosis and clinical evaluation of primary Sjögren's syndrome (pSS). METHODS: SE examination of major salivary glands was conducted for 79 pSS patients, 39 disease controls and 15 healthy subjects. Elastographic images were determined with a qualitative 4-point scoring method. Receiver operating characteristic (ROC) curve was employed to evaluate the performance of the elasticity scoring method and the best cut-off value was determined. The associations between elasticity scores and disease characteristics were analysed to evaluate the clinical value of SE for pSS. RESULTS: Elasticity scores of parotid and submandibular glands in pSS group were significantly higher than those in the non-pSS group (p<0.001). The sum of the scores of all four glands provided the largest AUC-ROC (0.916, 95% CI 0.87-0.962), compared with that of bilateral parotid glands (0.857, 95% CI 0.794-0.919) and that of bilateral submandibular glands (0.783, 95% CI 0.704-0.863). The optimal cut-off value was 9 for combined evaluation of all four glands (81% sensitivity and 87% specificity, respectively). The elasticity scores of parotid glands in patients with disease duration >10 years experienced significant difference as compared to patients with disease duration ≤5 years and 5-10 years respectively (p=0.007, 0.009, respectively), whereas it presented no variations between the disease duration ≤5 years and 5-10 years (p=0.952). CONCLUSIONS: Sonoelastography, performed simultaneously with ultrasonography, is an additional tool for the assessment of the salivary glands in patients with pSS. The elasticity is closely associated with disease duration.

Toll-like receptors expressed by synovial fibroblasts perpetuate Th1 and th17 cell responses in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial fibroblast hyperplasia and bone and cartilage erosion. Synovial fibroblast- and T cell-mediated inflammation plays crucial roles in the pathogenesis of RA. However how this inflammation is initiated, propagated, and maintained remains controversial. Here, we systemically examined the contribution of toll-like receptors (TLRs) to the inflammatory mediator production as well as Th1 and Th17 cell hyperactivity in RA. Our results show that rheumatoid arthritis synovial fibroblasts (RASF) express a series of TLRs, including TLR2, TLR3, TLR4, and TLR9, with the predominant expression of TLR3. Moreover, the expression levels of these TLRs were higher than those in osteoarthritis synovial fibroblasts (OASF). Ligation of TLR3, as well as TLR2 and TLR4, resulted in vigorous production of inflammatory cytokines, matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF) in RASF, with activation of the NF-κB, MAPK, and IRF3 pathways. More important, activation of these TLRs expressed by RASF exacerbated inflammatory Th1 and Th17 cell expansion both in cell-cell contact-dependent and inflammatory cytokine-dependent manners, which induced more IFN-γ and IL-17 accumulation. Targeting TLRs may modulate the inflammation in RA and provide new therapeutic strategies for overcoming this persistent disease.

Increased IL-33 in synovial fluid and paired serum is associated with disease activity and autoantibodies in rheumatoid arthritis.

OBJECTIVES: IL-33, a newly found cytokine which is involved in joint inflammation, could be blocked by a decoy receptor-sST2. The expression and correlation of IL-33 and sST2 in rheumatoid arthritis (RA) are of great interest. METHODS: Synovial fluid (SF) was obtained from 120 RA and 30 osteoarthritis (OA) patients, and paired sera were collected from 54 of these RA patients. The levels of IL-33 and sST2 were measured by ELISA. RESULTS: SF IL-33 was significantly higher in RA than in OA, which was correlated with disease activity score 28, erythrocyte sedimentation rate, rheumatoid factor (RF)-IgM, RF-IgG, glucose phosphate isomerase (GPI), and immunoglobulin. Serum IL-33 was correlated positively with SF IL-33 in RA. Furthermore, it was correlated with RF-IgM and GPI. sST2 was partly detectable in RA (13 out of 54, 24.1%), while not in OA. Serum sST2 in RA had no significant correlation with serum IL-33 or SF IL-33. However, SFs from both RA and OA patients did not express sST2. CONCLUSIONS: This study supported that IL-33 played an important role in the local pathogenesis of RA. Considering the tight correlation between IL-33 and clinical features, it may become a new target of local treatment.

[Diagnostic significance of serum allergen detection in diagnosis of allergic rhinitis and bronchial asthma].

OBJECTIVE: To analyze the diagnostic significance of serum total IgE, specific IgE (SIgE), Phadiatop, and eosinophil cationic protein (ECP) in allergic rhinitis and bronchial asthma. METHODS: The serum total IgE, SIgE , and Phadiatop were tested in 122 patients with allergic rhinitis. The ECP, SIgE, and Phadiatop were tested in 135 patients with bronchial asthma. Forty healthy persons were used as controls. The serum total IgE were tested by electrochemiluminescence. The serum Phadiatop, ECP, and SIgE were tested by fluorescent-enzyme linked immunosorbent assay. RESULTS: The serum total IgE positive rate of the 122 allergic rhinitis patients was 37.7%, significantly higher than that of the healthy controls (2.5%, chi2 = 18.13, P < 0.01). The specificity of total IgE of the allergic rhinitis patients were 97.5%. The serum ECP positive rate of the bronchial asthma patients was 65.9%, significantly higher than that of the healthy controls (20.0%, chi2 = 26.34, P < 0.01). The sensitivity and specificity of the bronchial asthma patients were 65.9% and 80.0%. The Phadiatop positive rates of the allergic rhinitis and the bronchial asthma patients were 50.0% and 31.9% respectively, both significantly higher than that of the control (0, chi2 = 32.08, 16.89, both P < 0.01). Most kinds of SIgE were from the allergens, such as dust mite, dust, and Artemisia etc. CONCLUSION: Increase of serum ECP level is an important indicator of airway inflammation activity and inflammation serious degree in the bronchial asthma patients. The increase of serum total IgE has an important diagnostic significance in allergic rhinitis. It is important to detect SIgE and Phadiatop in diagnosis and monitoring of allergic rhinitis and bronchial asthma.