Long-term outcomes of refractory Takayasu arteritis patients treated with biologics including ustekinumab.

OBJECTIVES: Biologics have been used to treat refractory Takayasu arteritis (TAK), but their efficacy and safety have not been sufficiently evaluated. METHODS: We extracted clinical information from medical records for TAK patients who were treated with biologics including ustekinumab (UST) at Kyoto University Hospital. We also analysed the patient's genetic backgrounds. RESULTS: Of 163 cases, 12 (7.4%) were treated with infliximab, tocilizumab, or UST (n = 3). Erythrocyte sedimentation rate (ESR), C-reactive protein levels (CRP), and prednisolone (PSL) dose were significantly decreased 12 months after the initiation of biologics. When compared with the 15 patients who were only treated with immunosuppressants (IS group), the change in ESR from baseline was significantly lower in the biologics group than in the IS group (-2 mm/h, p = .005). The proportion of patients with HLA-B*52 and the risk-type alleles of the SNP were similar in both groups. Among the biologics, TCZ showed the highest continuation rate. UST exhibited marginal effects on reducing ESR, CRP levels, and PSL dose. No adverse events were observed in patients with UST for approximately 3 years. CONCLUSIONS: Biological treatments resulted in a reduction in inflammatory markers and PSL dose in refractory TAK patients.

Feasibility of patient-oriented ultrasound joint selection: Cross-sectional observational study on rheumatoid arthritis.

Objective: Ultrasonography (US) is a useful tool for evaluating the activity of rheumatoid arthritis (RA) patients. As the systemic evaluation of many joints is time-consuming, a method to evaluate this activity with a smaller number of joints is needed. The aim of this study was to clarify whether the number of joints assessed may be reduced using patient-oriented joint selection.Methods: A total of 492 RA patients were recruited at Kyoto University Hospital. Bilateral metacarpophalangeal (MCP), (proximal) interphalangeal (PIP/IP), and wrist joints were evaluated by US. Gray scale and power Doppler imaging findings were scored by a 0-3 semi-quantitative method. Clinical assessments were performed by physicians who were blind to US results, and a questionnaire on subjective symptoms was collected from each patient.Results: The correlation between the US score of all 22 joints (US22) and patient-oriented painful joints (PtUS) or physician-oriented tender and/or swollen joints were moderate (Spearman's ρ = 0.435) and weak (ρ = 0.383), respectively. These correlations were weaker than that between the total US score of 5 preselected joints (unilateral 2MCP, 3MCP, 2PIP, 3PIP, and the wrist) and US22 (ρ = 0.813). However, when focusing on patients whose painful joints were 5 and more, the correlation between PtUS and US22 was markedly stronger (ρ = 0.757).Conclusion: Patient-oriented joint selection reflected actual joint inflammation to some extent. However, excessive reductions in the number of joints assessed need to be avoided even if patients do not have arthralgia because of the potential for underestimations.

Increased number of T cells and exacerbated inflammatory pathophysiology in a human IgG4 knock-in MRL/lpr mouse model.

Immunoglobulin (Ig) G4 is an IgG subclass that can exhibit inhibitory functions under certain conditions because of its capacity to carry out Fab-arm exchange, inability to form immune complexes, and lack of antibody-dependent and complement-dependent cytotoxicity. Although several diseases have been associated with IgG4, its role in the disease pathogeneses remains unclear. Since mice do not express an IgG subclass that is identical to the human IgG4 (hIgG4), we generated hIGHG4 knock-in (KI) mice and analyzed their phenotypes. To preserve the rearrangement of the variable, diversity, and joining regions in the IGH gene, we transfected a constant region of the hIGHG4 gene into C57BL/6NCrSlc mice by using a gene targeting method. Although the mRNA expression of hIGHG4 was detected in the murine spleen, the serum level of the hIgG4 protein was low in C57BL/6-IgG4KI mice. To enhance the production of IgG4, we established an MRL/lpr-IgG4KI mice model by backcrossing. These mice showed a high IgG4 concentration in the sera and increased populations of IgG4-positive plasma cells and CD3+B220+CD138+ T cells in the spleen. Moreover, these mice showed aggravated inflammation in organs, such as the salivary glands and stomach. The MRL/lpr-IgG4KI mouse model established in the present study might be useful for studying IgG4-related disease, IgG4-type antibody-related diseases, and allergic diseases.

A case of fatal osteolytic hypercalcemia complicated with IgG4-related ophthalmic disease leading to renal failure.

A 40-year-old male was hospitalized with renal impairment and severe hypercalcemia. His concentration of serum IgG4 was high, but serum whole PTH, 1-25(OH)2 vitamin D3 and PTHrP were not elevated. Computed tomography showed swelling of the bilateral lacrimal glands and systemic lymphadenopathy. The histological findings of lacrimal gland biopsy fulfilled the diagnostic criteria of IgG4-related ophthalmic disease (IgG4ROD). Bone scintigraphy showed increased ectopic uptake in the stomach, heart, lungs, and kidneys. He died on day 16 of admission, although the therapies for hypercalcemia were continued. Autopsy results showed an increase of osteoclasts in the bone marrow and metastatic calcification in multiple organs, and excluded from the differential diagnosis other disorders which present lymph-node swelling and hypercalcemia such as cancer, lymphoma, Castleman's disease, and sarcoidosis. He was given a diagnosis of IgG4ROD with osteolytic hypercalcemia.