Can transbronchial lung cryobiopsy benefit adaptive treatment strategies in connective tissue disease-associated interstitial lung disease?

BACKGROUND: Some patients with connective tissue disease (CTD)-associated interstitial lung disease (ILD) progress to pulmonary fibrosis over their disease course despite initial improvement, potentially indicating a poor prognosis. Transbronchial lung cryobiopsy (TBLC) is a new bioptic approach used in diffuse parenchymal lung diseases. This study of CTD-ILD assessed the utility of TBLC in determining therapeutic decision-making strategies. METHODS: We analyzed medical records of 31 consecutive CTD-ILD patients who underwent TBLC focusing on radio-pathological correlation and disease course. A TBLC-based usual interstitial pneumonia (UIP) score was used that assessed three morphologic descriptors: i) patchy fibrosis, ii) fibroblastic foci, and iii) honeycombing. RESULTS: Among the patients with CTD-ILD, 3 had rheumatoid arthritis, 2 systemic sclerosis, 5 polymyositis/dermatomyositis, 8 anti-synthetase syndrome, 6 Sjögren's syndrome, and 5 had microscopic polyangiitis. Pulmonary function test results showed a mean %FVC of 82.4% and %DLCO of 67.7%. Among the 10 CTD patients and TBLC-proven pathological UIP, 3 patients had prominent inflammatory cells in addition to a framework of UIP, and pulmonary function of most patients improved with anti-inflammatory agents. Six (40%) of 15 patients with TBLC-based UIP score ≥ 1 had a progressive disease course during follow-up, of whom 4 patients received anti-fibrotic agents. CONCLUSIONS: TBLC in patients with CTD-ILD can help determine an appropriate medication strategy, particularly when UIP-like lesions are present. TBLC may be useful when judging which agents to prioritize, anti-inflammatory or anti-fibrotic, is difficult. Moreover, additional information from TBLC may be beneficial when considering early intervention with anti-fibrotic agents in clinical practice.

Prognostic value of radiological findings indeterminate for UIP pattern and anterior upper lobe honeycomb-like lesion in chronic fibrosing interstitial lung disease associated with MPO-ANCA.

BACKGROUND: Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is often positive in patients with interstitial lung disease (ILD), which is also often present in patients with microscopic polyangiitis (MPA). A possible association between MPO-ANCA, MPA, and idiopathic ILD remains unclear. The objective of this study was to determine whether high-resolution computed tomography (HRCT) classification based on recent idiopathic pulmonary fibrosis guideline and specific CT findings can obtain new knowledge of prognostic factors in all MPO-ANCA-positive patients with ILD including both idiopathic ILD and MPA-ILD. METHODS: We analyzed 101 consecutive MPO-ANCA-positive patients with respiratory disease. We assessed the diagnostic accuracy of CT findings, HRCT pattern, and specific radiological signs. Prognostic predictors were determined using Cox regression models. RESULTS: Subjects with chronic ILD included 22 patients with MPA-ILD and 39 patients with ILD but without MPA. A quarter of the patients were radiological indeterminate for usual interstitial pneumonia (UIP) pattern, which resulted in a better prognosis than that for UIP pattern. "Increased attenuation around honeycomb and traction bronchiectasis" and "anterior upper lobe honeycomb-like lesion" were found to be highly frequent radiological findings (39% and 30%, respectively). In addition, the latter finding was a significant negative prognostic factor. CONCLUSIONS: Radiological indeterminate for UIP was a useful HRCT classification in MPO-ANCA-positive patients with ILD. In addition, anterior upper lobe honeycomb-like lesion was found to be specific radiological finding that was a significant prognostic factor. The present results might aid in the assessment of appropriate strategies of diagnosis in these patients.

The potential utility of anterior upper lobe honeycomb-like lesion in interstitial lung disease associated with connective tissue disease.

BACKGROUND: Interstitial lung disease (ILD) is associated with high morbidity and mortality in patients with connective tissue disease (CTD). Because some patients with CTD overlap present with ILD first, with CTD diagnosed later, specific radiologic signs are needed to help differentiate each CTD or CTD-ILD from idiopathic ILD. OBJECTIVES: To determine whether specific CT findings can help differentiate CTD as rheumatoid arthritis (RA), systemic sclerosis (SSc), or polymyositis/dermatomyositis (PM/DM). METHODS: We analyzed 143 consecutive ILD patients with RA, SSc, or PM/DM. We assessed diagnostic accuracy of CT findings of CTD-ILD, CT pattern, and signs including "anterior upper lobe honeycomb-like lesion" and "low attenuation area (LAA) within an interstitial abnormality" for each CTD-ILD. Prognostic predictors were determined using Cox regression models. RESULTS: Subjects were 78 patients with RA-ILD, 38 with SSc-ILD, 24 with PM/DM-ILD, and 3 with overlapping CTD-ILD. High frequency of anterior upper lobe honeycomb-like lesion suggests that CTD-ILD is due to RA-ILD (22%) rather than SSc-ILD (8%) or PM/DM-ILD (8%), whereas LAA within an interstitial abnormality suggests that CTD-ILD is due to SSc-ILD (26%) rather than RA-ILD (4%) or PM/DM-ILD (0%). Multivariate analysis showed that while not associated with survival, current or ex-smoker, honeycombing, and acute exacerbation were negative prognostic factors of mortality. CONCLUSIONS: The tendency is high for RA-ILD, in which anterior upper lobe honeycomb-like lesion is a specific feature, to show UIP or NSIP/UIP pattern, combined emphysema, and honeycombing; SSc-ILD to show NSIP pattern and LAA within an interstitial abnormality; and PM/DM-ILD to show NSIP pattern and non-honeycombing.

Impact of radiological honeycombing in rheumatoid arthritis-associated interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is the most common and important pulmonary manifestation of rheumatoid arthritis (RA). A radiological honeycomb pattern has been described in diverse forms of ILD that can impact survival. However, the clinical course and sequential radiological changes in the formation of the honeycomb pattern in patients with RA-ILD is not fully understood. METHODS: We evaluated the sequential changes in computed tomography findings in 40 patients with chronic forms of RA-ILD without the honeycomb pattern at initial diagnosis. We classified the patients into the Non-honeycomb group and Honeycomb group, and then analyzed the characteristics and prognosis of the two groups. The term "honeycomb formation" indicated a positive finding of honeycombing on any available follow-up CT. RESULTS: Our RA-ILD cohort included patients with probable usual interstitial pneumonia (UIP) (35%), nonspecific interstitial pneumonia (NSIP) (20%), and mixed NSIP/UIP (45%). Among all RA-ILD patients, 16 (40%) showed honeycomb formation on follow-up CT (median time between initial and last follow-up CT was 4.7 years). Patient characteristics and prognosis were not significantly different between the Non-honeycomb and Honeycomb groups. However, Kaplan-Meier survival curve for the time from the date of honeycomb formation to death showed a poor median survival time of 3.2 years. CONCLUSIONS: A certain number of patients with RA-ILD developed a honeycomb pattern during long-term follow-up, regardless of whether they had UIP or NSIP. Prognosis in the patients with characteristics of both progressive ILD and honeycomb formation could be poor. Although radiological findings over the disease course and clinical disease behavior in RA-ILD are heterogenous, clinicians should be alert to the possibility of progressive disease and poor prognosis in patients with RA-ILD who form a honeycomb pattern during follow-up observation.

Predictive factors of mortality in rheumatoid arthritis-associated interstitial lung disease analysed by modified HRCT classification of idiopathic pulmonary fibrosis according to the 2018 ATS/ERS/JRS/ALAT criteria.

BACKGROUND: Interstitial lung disease (ILD) is associated with high morbidity and mortality in rheumatoid arthritis (RA). Although usual interstitial pneumonia (UIP) pattern was reported as a poor prognostic factor, in clinical practice, we often cannot classify high-resolution computed tomography (HRCT) patterns specifically as UIP or nonspecific interstitial pneumonia (NSIP). This study of RA-ILD aimed to elucidate prognosis by using our modified HRCT pattern classification according to the latest guideline on idiopathic pulmonary fibrosis (IPF). METHODS: We analysed the medical records of 96 consecutive patients diagnosed as having RA-ILD. The modified HRCT classifications were defined as definite UIP, probable UIP, indeterminate for UIP (i.e., early UIP or NSIP/UIP), NSIP, organizing pneumonia (OP), NSIP+OP, and unclassifiable. Predictors of prognosis were determined using Cox regression models. RESULTS: Our RA-ILD cohort included definite UIP (21%), probable UIP (20%), indeterminate for UIP (30%) including NSIP/UIP (27%), alternative diagnosis (29%) including NSIP (14%), and other patterns. Interrater agreement for HRCT pattern was good (κ=0.75). Multivariate analysis showed that older age, history of acute exacerbation, and radiological honeycombing were negative prognostic factors of mortality. CONCLUSIONS: NSIP/UIP pattern of indeterminate for UIP was the major pattern in RA-ILD. Although classifications of HRCT patterns were not related to survival, the presence of radiological honeycombing could be a useful predictor of poor prognosis, and acute exacerbation of ILD can seriously impact patient survival regardless of the presence of a UIP or indeterminate for UIP pattern. Our modified HRCT classification based on the latest IPF guideline might be useful to assess appropriate strategies of diagnosis in future RA-ILD studies, and radiological honeycombing could better predict poor prognosis rather than HRCT pattern.

A case of anti-melanoma differentiation-associated gene 5 antibody-positive interstitial lung disease complicated with tracheobronchial ulcers.

We herein report the first case, to our knowledge, of tracheobronchial ulcer with anti-melanoma differentiation-associated gene 5 (anti-MDA 5) antibody-positive interstitial lung disease (ILD). A 53-year-old man complained of shoulder and wrist pain and was suspected of having polymyalgia rheumatica at another hospital. Thereafter, treatment with prednisolone was started. Although his arthralgia improved, he suffered from progressive dyspnea on exertion and an abnormal shadow was noted on chest X-ray, so he was transferred to our hospital. Chest computed tomography scan revealed ground-glass opacities and intralobular septal thickening. We diagnosed him as having clinically amyopathic dermatomyositis associated with ILD based on the specific skin findings and elevated anti-MDA 5 antibody titer. Fiberoptic bronchoscopy showed ulcerations of the trachea and bronchus. Treatment with dose increments of prednisolone combined with other immunosuppressive drugs resulted in improvement of his respiratory condition and tracheobronchial lesions. Clinicians should be aware that tracheobronchial ulcers can be associated with anti-MDA 5 antibody-positive interstitial lung disease.

A multicenter phase II prospective clinical trial of glucocorticoid for patients with untreated IgG4-related disease.

OBJECTIVE: Although glucocorticoids are effective for patients with IgG4-related disease, the treatment has not yet been standardized. Therefore, the treatment strategy should be established. PATIENTS AND METHODS: Patients who fulfilled the comprehensive diagnostic criteria for definite IgG4-related disease were started on prednisolone (0.6 mg/kg body weight) with the dose reduced every two weeks. The subsequent maintenance dose and need for prednisolone were determined for individual patients. The primary endpoint was the complete remission (CR) rate at one year. Secondary endpoints included overall response rate (ORR), the maintenance dose, the relapse rate, and adverse events. RESULTS: This study enrolled 61 patients. After clinicopathological review, three patients were excluded, and one, 13, and 44 patients were diagnosed with probable, possible, and definite IgG4-related disease, respectively. Of the 44 patients with definite IgG4-RD, 29 (65.9%) achieved CR, and the ORR was 93.2%. No patient was refractory to primary treatment. The most frequent adverse events were glucose intolerance. Six patients relapsed. CONCLUSIONS: Glucocorticoid treatment is usually effective for patients with IgG4-RD, and we should examine the possibility of other disorders when a patient is glucocorticoid refractory. Some patients are misdiagnosed, making central clinicopathological review of diagnosis very important in conducting clinical studies.

Thermal Disparity between Fingers after Cold-water Immersion of Hands: A Useful Indicator of Disturbed Peripheral Circulation in Raynaud Phenomenon Patients.

OBJECTIVE: To devise an effective method to assess the peripheral circulation using an infrared thermographic analysis. METHODS: Sequential measurements of the skin temperature before and after cold-water immersion of the hands were analyzed by a thermographic examination in healthy controls and patients diagnosed to have Raynaud phenomenon (RP). The skin temperatures of the dorsum of all fingernail folds and the metacarpophalangeal (MCP) joints were measured at baseline. Then the hands were immersed in 10°C water for 10 s, and the skin temperatures were measured at 0, 3, 5, 10, 15, 20 and 30 min after immersion. The mean temperature, recovery rate and disparity (coefficient of variation) of the nail fold temperatures were calculated. The distal-dorsal difference (DDD) was calculated by subtracting the mean MCP temperature from the mean nail fold temperature. Receiver operating characteristic (ROC) curves were generated to compare these parameters in terms of their capability to differentiate patients with RP. RESULTS: Thirty-one RP patients and 25 controls were included in the study. The baseline nail fold temperature was significantly lower in RP patients than in the controls. The RP patients had a lower recovery rate, lower DDD and higher disparity than the controls. The disparity and DDD were negatively correlated (r=-0.63, p<0.01), whereas the recovery rate and DDD were positively correlated (r=0.91, p<0.01). The ROC curve analysis revealed that the disparity in nail fold temperature effectively differentiated RP patients from controls (area under the curve: recovery rate 0.72; disparity 0.88; DDD 0.79). CONCLUSION: The temperature disparity between fingers is a useful thermographic parameter for evaluating disturbed peripheral circulation in patients with Raynaud phenomenon.

Atypical Subacute Recurrence of Catastrophic Antiphospholipid Syndrome in a Japanese Female Patient.

Catastrophic antiphospholipid syndrome (CAPS) survivors rarely relapse. We herein report a case of a second CAPS episode with an unusual subacute course and no microangiopathic hemolytic anemia (MAHA), a common CAPS symptom. During the first episode, the 69-year-old woman responded well to high-dose glucocorticoids and plasma exchange. On relapse, these treatments plus rituximab were ineffective and she died of multi-organ failure and bacterial cholangitis. The absence of MAHA and a subacute course do not exclude a CAPS recurrence.

Involvement of CD161+ Vδ1+ γδ T cells in systemic sclerosis: association with interstitial pneumonia.

OBJECTIVE: Interstitial pneumonia (IP) is a chronic progressive interstitial lung disease associated with high mortality and poor prognosis. However, the pathogenesis of IP remains to be elucidated. The aim of this study was to clarify the role of CD161(+) Vδ1(+) γδ T cells in SSc patients with IP. METHODS: The proportion of CD161(+) Vδ1(+) γδ T cells in peripheral blood mononuclear cells (PBMCs) and serum sialylated carbohydrate antigen (KL-6) levels were determined. GeneChip analysis was performed with CD161(-) and CD161(+) Vδ1(+) γδ T cells. Cytokine and chemokine expression from CD161(+) Vδ1(+) γδ T cells was measured and used to evaluate the effect of culture supernatant on fibroblast proliferation. RESULTS: The proportion of CD161(+) Vδ1(+) γδ T cells was significantly higher in SSc than healthy controls (HCs) and correlated negatively with serum KL-6 levels in IP-positive SSc patients. The gene and mRNA expression level of chemokine ligand 3 (CCL3) was markedly higher in CD161(+) Vδ1(+) γδ T cells than in CD161(-) Vδ1(+) γδ T cells. CD161(+) Vδ1(+) γδ T cells in IP-positive SSc patients showed higher production of CCL3 and lower production of IFN-γ than in HCs. Culture supernatant derived from IP-negative and IP-positive SSc patients promoted fibroblast proliferation, whereas that from HCs did not. CONCLUSION: The small proportion and the altered cell functions of CD161(+) Vδ1(+) γδ T cells among PBMCs in SSc patients play a role in the pathogenesis of IP. These findings suggest that CD161(+) Vδ1(+) γδ T cells may play a regulatory role in the pathogenesis of IP in SSc patients via IFN-γ production.

Clinicopathological features of IgG4-related disease complicated with orbital involvement.

OBJECTIVE: IgG4-related disease (IgG4-RD) is characterized by IgG4-positive plasmacytic infiltration and fibrosis in various organs. Orbital involvement in IgG4-RD includes lacrimal glands, extra-ocular muscles, trigeminal nerve and other parts of the orbit. Immunohistochemical staining is used to diagnose IgG4-RD in patients with orbital inflammation. The purpose of this retrospective study was to clarify the clinicopathological features of IgG4-RD complicated with orbital involvement. METHODS: We examined the clinical features, pathological findings and response to treatment in nine patients with IgG4-RD who underwent orbital tissue biopsy between April 2010 and August 2012 at the University of Tsukuba Hospital. RESULTS: Among the nine patients, eight had dacryoadenitis, one had infraorbital nerve swelling, and another one had IgG4-related orbital inflammation. Involvement of other organs was identified in all patients, including involvement of the salivary glands, lymph nodes, lung, kidney and para-aorta. In all patients, biopsy samples from orbital tissues showed lymphoplasmacytic infiltration and fibrosis, and IgG4-positive/IgG-positive plasmacyte ratio of > 40%. All patients were treated with prednisolone (0.6 mg/kg/day) and responded well in early phase, although relapse was noted in two patients following tapering of prednisolone, evident by swelling of lacrimal glands. CONCLUSION: Patients with IgG4-RD complicated with orbital involvement often present with involvement of other organs. The histopathological findings of orbital tissue match the characteristic features of IgG4-RD. Corticosteroid is effective for orbital and systemic involvement in IgG4-RD.

Analysis of subclinical synovitis detected by ultrasonography and low-field magnetic resonance imaging in patients with rheumatoid arthritis.

OBJECTIVE: To assess the utilities of ultrasonography (US) and low-field magnetic resonance imaging (compacTscan, cMRI) in the diagnosis of subclinical synovitis of hand joints of patients with rheumatoid arthritis (RA). METHODS: A total of 1,540 joints of 77 RA patients were examined clinically, using US, using cMRI, and the baseline X-ray examination was performed. Clinical synovitis was defined as joint tenderness or swelling. Subclinical synovitis was diagnosed by US and by cMRI. The incidence of bone erosion and joint space narrowing was assessed by X-ray examination performed at approximately 40 weeks of follow-up. RESULTS: Of the hand joints examined, 294 (19.1 %) were diagnosed with clinical synovitis, and 218 joints (14.1 %) were diagnosed with subclinical synovitis. The remaining 1,028 joints (66.8 %) were synovitis-free on clinical examination and imaging. For the diagnosis of subclinical synovitis, cMRI (11.4 %) was significantly more sensitive than power Doppler signals detected by US (US-PD; 6.8 %) (P < 0.01), and the combination of US-PD and cMRI was more useful (14.1 %) than US-PD or cMRI alone (P < 0.05). Follow-up X-ray examination of 600 joints showed a significantly higher incidence of bone erosion in joints with subclinical synovitis than in synovitis-free joints (P < 0.05). CONCLUSION: US-PD and cMRI are useful for detecting subclinical synovitis in patients with RA. Subclinical synovitis of the small joints of the hand can progress to bone destruction.

Therapeutic efficacy of tocilizumab in patients with rheumatoid arthritis refractory to anti-tumor-necrosis-factor inhibitors: 1 year follow-up with low-field extremity MRI.

OBJECTIVE: Tocilizumab (TCZ) is effective in patients with rheumatoid arthritis (RA) who are refractory to anti-tumor-necrosis-factor (anti-TNF) biologics. The Rheumatoid Arthritis Society Disease Activity Score in 28 Joints (DAS28) is used to evaluate the response to TCZ. However, DAS28 is inappropriate marker because TCZ normalizes C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the early stage of treatment. The aim of our study was to test the usefulness of magnetic resonance imaging (MRI)-based markers of response to TCZ treatment. METHODS: Nine patients with RA who were refractory to anti-TNF inhibitors (six to infliximab, one to etanercept, one to adalimumab, and one to both) were assessed. MRI images of both hands were obtained by low-field extremity MRI at baseline, 20, and 44 weeks of treatment, in addition to assessment with DAS28-ESR. The effect of TCZ on RA was examined by compact MRI score (cMRIS). RESULTS: All patients showed good or moderate response to TCZ treatment, as evaluated by significant reduction in DAS28-ESR at both 20 and 44 weeks (p < 0.001, each, relative to baseline). In contrast, MRI-based indexes (e.g., cMRIS, synovitis, edema, erosion scores) improved significantly at 44 weeks but not at 20 weeks. CONCLUSION: Differences in response to TCZ therapy were determined based on the method of evaluation, suggesting that MRI-based markers are potentially useful for evaluating RA response to TCZ therapy.

Activation of Invariant NKT cells with glycolipid ligand α-galactosylceramide ameliorates glucose-6-phosphate isomerase peptide-induced arthritis.

OBJECTIVE: Invariant natural killer T (iNKT) cells regulate collagen-induced arthritis (CIA) when activated by their potent glycolipid ligand, alpha-galactosylceramide (α-GalCer). Glucose-6-phosphate isomerase (GPI)-induced arthritis is a closer model of human rheumatoid arthritis based on its association with CD4+ T cells and cytokines such as TNF-α and IL-6 than CIA. Dominant T cell epitope peptide of GPI (GPI325-339) can induce arthritis similar to GPI-induced arthritis. In this study, we investigated the roles of activation of iNKT cells by α-GalCer in GPI peptide-induced arthritis. METHODS: Arthritis was induced in susceptible DBA1 mice with GPI peptide and its severity was assessed clinically. The arthritic mice were treated with either the vehicle (DMSO) or α-GalCer. iNKT cells were detected in draining lymph nodes (dLNs) by flow cytometry, while serum anti-GPI antibody levels were measured by enzyme-linked immunosorbent assay. To evaluate GPI peptide-specific cytokine production from CD4+ T cells, immunized mice were euthanized and dLN CD4+ cells were re-stimulated by GPI-peptide in the presence of antigen-presenting cells. RESULTS: α-GalCer induced iNKT cell expansion in dLNs and significantly decreased the severity of GPI peptide-induced arthritis. In α-GalCer-treated mice, anti-GPI antibody production (total IgG, IgG1, IgG2b) and IL-17, IFN-γ, IL-2, and TNF-α produced by GPI peptide-specific T cells were significantly suppressed at day 10. Moreover, GPI-reactive T cells from mice immunized with GPI and α-GalCer did not generate any cytokines even when these cells were co-cultured with APC from mice immunized with GPI alone. In vitro depletion of iNKT cells did not alter the suppressive effect of α-GalCer on CD4+ T cells. CONCLUSION: α-GalCer significantly suppressed GPI peptide-induced arthritis through the suppression of GPI-specific CD4+ T cells.

A case of disseminated sporotrichosis treated with prednisolone, immunosuppressants, and tocilizumab under the diagnosis of rheumatoid arthritis.

We encountered a disseminated sporotrichosis patient with polyarthritis and progressive skin ulcers, who had been previously treated with prednisolone, tocilizmab, tacrolims, and cyclophosphamide under the diagnosis of rheumatoid arthritis in another hospital. Making the diagnosis of leukocytoclasticvasculitis based on the clinical observation of skin ulcers, we intensified immunosuppressive therapy. Unfortunately, the patient developed septic shock. Blood culture revealed that the pathogenic organism was sporothrixschenckii. Any case of intractable arthritis or skin ulcers, which does not improve, despite adequate immunosuppressive therapy, is likely to be suspicious of sporotrichosis.

Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease.

IgG4-related disease is a new disease classification established in Japan in the 21st century. Patients with IgG4-related disease display hyper-IgG4-gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and good response to glucocorticoids. Since IgG4 overexpression is also observed in other disorders, it is necessary to diagnose IgG4-related disease carefully and correctly. We therefore sought to determine cutoff values for serum IgG4 and IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related disease. Patients and Methods. We retrospectively analyzed serum IgG4 concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of 132 patients with IgG4-related disease and 48 patients with other disorders. Result. Serum IgG4 >135 mg/dl demonstrated a sensitivity of 97.0% and a specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively. IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of 94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in severely fibrotic parts of tissues. Conclusion. Although a recent unanimous consensus of all relevant researchers in Japan recently established the diagnostic criteria for IgG4-related disease, findings such as ours indicate that further discussion is needed.

[Evaluation of joint inflammation by MRI in patients with RA].

We compared the characteristics of MRI imaging and US imaging on joint inflammation in patients with rheumatoid arthritis (RA) . MRI imaging is worth for diagnosis of RA at the early stage, evaluation of drug treatment effects, and a new measure for true remission. US imaging is also useful for estimation of therapy and a criteria for complete remission, and cheep machine. We hope that both imaging technologies will be a standard for diagnosis and therapy evaluation in RA patients.

Involvement of NK 1.1-positive γδT cells in interleukin-18 plus interleukin-2-induced interstitial lung disease.

Interstitial lung disease (ILD) is induced by various factors in humans. However, the exact mechanism of ILD remains elusive. This study sought to determine the role of natural killer (NK) 1.1(+) γδT cells in ILD. The injection of IL-18 plus IL-2 (IL-18/IL-2) into C57BL6 (B6) mice induced acute ILD that resembled early-stage human ILD. An accumulation of NK1.1(+) γδT cells similar to NK cells was evident in the lungs. The T Cell Receptor (TCR) Vγ and Vδ repertoires of NK1.1(+) γδT cells indicated polyclonal expansion. The expression of IL-2 receptor ß (Rß) and IL-18Rß in NK1.1(+) γδT cells was higher than in NK1.1(-) γδT cells. IL-18/IL-2 stimulated the proliferation of NK1.1(+) γδT cells, but not NK1.1(-) γδT cells. The IL-18/IL-2-stimulated NK1.1(+) γδT cells produced higher concentrations of IFN-γ than did NK1.1(-) γδT cells. Moreover, NK1.1(+) γδT and NK1.1(-) γδT cells constituted completely different cell populations. The IL-18/IL-2-induced ILD was milder in TCRδ(-/-) and IFN-γ(-/-) mice, compared with B6 mice. Furthermore, cell-transfer experiments demonstrated that NK1.1(+) γδT cells could induce the expansion of NK cells and IFN-γ mRNA in the lung by IL-18/IL-2. Our results suggest that NK1.1(+) γδT cells function as inflammatory mediators in the early phase of IL-18/IL-2-induced ILD.

Comparison of low-field dedicated extremity magnetic resonance imaging with articular ultrasonography in patients with rheumatoid arthritis.

To compare magnetic resonance imaging (MRI) and ultrasonography (US) in the detection of joint inflammation of rheumatoid arthritis (RA), 6 patients with RA were examined by US and low-field 0.3-T nonenhanced dedicated extremity MRI (compacTscan). All patients were females, with mean age of 50.2 years, mean disease duration of 13.5 years, and mean disease activity score (DAS)28-CRP of 1.78. Each patient was treated with either infliximab, etanercept, adalimumab, or tocilizumab. Intercarpal joints, radioulnar joints, second through fifth proximal interphalangeal (PIP) joints, and first through fifth metacarpophalangeal (MCP) joints (a total of 132 joints, 22 joints in each patient) were assessed by MRI for presence of joint inflammation. A total of 156 joints (24 first interphalangeal and radiocarpal joints plus the above 132 joints), were assessed by grayscale US (GS-US) and power Doppler US (PD-US) for presence of joint inflammation by two trained ultrasonographers. We assessed correlations between joint inflammations on MRI and GS-US/PD-US, and also interobserver correlation between the two ultrasonographers by calculating intraclass correlation coefficients (ICC). Synovial hypertrophy and/or synovial fluid was detected in 74/156 joints on GS-US, and synovitis was detected in 10/156 joints on PD-US and in 38/132 joints on MRI. Using PD-US as a reference, sensitivity of MRI in detection of synovitis was 80%. Using MRI as a reference, sensitivity of PD-US was 21%. Specificity of PD-US was higher than that of MRI. Overall agreement between GS-US and MRI and between PD-US and MRI was 0.56 and 0.76, respectively, suggesting that results of PD-US are close to those of MRI. ICC was 0.545 for GS-US and 0.807 for PD-US, suggesting specificity of PD-US in detecting joint inflammation. Our results show that findings of PD-US correlated with those of MRI. Low-field MRI and PD-US are useful tools for assessment of patients with RA.

New low-field extremity MRI, compacTscan: comparison with whole-body 1.5 T conventional MRI.

Low-field extremity magnetic resonance imaging (lfMRI) is currently commercially available and has been used clinically to evaluate rheumatoid arthritis (RA). However, one disadvantage of this new modality is that the field of view (FOV) is too small to assess hand and wrist joints simultaneously. Thus, we have developed a new lfMRI system, compacTscan, with a FOV that is large enough to simultaneously assess the entire wrist to proximal interphalangeal joint area. In this work, we examined its clinical value compared to conventional 1.5 tesla (T) MRI. The comparison involved evaluating three RA patients by both 0.3 T compacTscan and 1.5 T MRI on the same day. Bone erosion, bone edema, and synovitis were estimated by our new compact MRI scoring system (cMRIS) and the kappa coefficient was calculated on a joint-by-joint basis. We evaluated a total of 69 regions. Bone erosion was detected in 49 regions by compacTscan and in 48 regions by 1.5 T MRI, while the total erosion score was 77 for compacTscan and 76.5 for 1.5 T MRI. These findings point to excellent agreement between the two techniques (kappa = 0.833). Bone edema was detected in 14 regions by compacTscan and in 19 by 1.5 T MRI, and the total edema score was 36.25 by compacTscan and 47.5 by 1.5 T MRI. Pseudo-negative findings were noted in 5 regions. However, there was still good agreement between the techniques (kappa = 0.640). Total number of evaluated joints was 33. Synovitis was detected in 13 joints by compacTscan and 14 joints by 1.5 T MRI, while the total synovitis score was 30 by compacTscan and 32 by 1.5 T MRI. Thus, although 1 pseudo-positive and 2 pseudo-negative findings resulted from the joint evaluations, there was again excellent agreement between the techniques (kappa = 0.827). Overall, the data obtained by our compacTscan system showed high agreement with those obtained by conventional 1.5 T MRI with regard to diagnosis and the scoring of bone erosion, edema, and synovitis. We conclude that compacTscan is useful for diagnosis and estimation of disease activity in patients with RA.