Non-negligible ultrasonographic findings in sarcoid myositis: A case series and literature review.

Sarcoid myositis is a rare and often debilitating extrapulmonary manifestation of sarcoidosis that can be difficult to recognize without a prior sarcoidosis diagnosis. Sarcoidosis with muscle nodules or masses as the first symptom is the least common form, occurring in approximately 0.5%-2.3% of cases. This article presents four middle-aged female patients who initially sought medical attention for a lower limb mass. Ultrasound examinations revealed consistent characteristic changes indicative of myositis. All patients underwent ultrasound-guided muscle biopsy and were diagnosed with sarcoidosis. Therefore, ultrasonography plays a pivotal role as the primary diagnostic tool for the early detection of sarcoid myositis.

Case report and brief literature review: possible association of secukinumab with Guillain-Barré syndrome in psoriasis.

The etiology of Guillain-Barré syndrome (GBS) may be autoimmune. About two-thirds of patients typically experience their first symptoms within 5 days to 3 weeks after common infectious diseases, surgery, or vaccination. Infection is a triggering factor for over 50% of patients. In recent years, a growing number of studies have indicated that some immune checkpoint inhibitors and COVID-19 may also contribute to the occurrence of GBS. However, drugs are considered a rare cause of GBS. The patient in our case was a 70-year-old man who developed GBS after initiating secukinumab for psoriasis. Upon diagnosis suggesting a potential association between secukinumab and the development of GBS, as per the Naranjo adverse drug reaction (ADR) probability scale, we decided to discontinue the drug. Following this intervention, along with the administration of immunoglobulin, the patient exhibited a significant improvement in extremity weakness. The association of GBS with secukinumab treatment, as observed in this case, appears to be uncommon. The underlying mechanisms that may link secukinumab to the development of GBS are not yet fully understood and warrant further scientific inquiry and rigorous investigation. However, we hope that this report can raise greater awareness and vigilance among medical professionals to enhance the safety of patients' medication.

Toxoplasma gondii chitinase-like protein TgCLP1 regulates the parasite cyst burden.

Toxoplasma, an important intracellular parasite of humans and animals, causes life-threatening toxoplasmosis in immunocompromised individuals. Although Toxoplasma secretory proteins during acute infection (tachyzoite, which divides rapidly and causes inflammation) have been extensively characterized, those involved in chronic infection (bradyzoite, which divides slowly and is surrounded by a cyst wall) remain uncertain. Regulation of the cyst wall is essential to the parasite life cycle, and polysaccharides, such as chitin, in the cyst wall are necessary to sustain latent infection. Toxoplasma secretory proteins during the bradyzoite stage may have important roles in regulating the cyst wall via polysaccharides. Here, we focused on characterizing the hypothetical T. gondii chitinase, chitinase-like protein 1 (TgCLP1). We found that the chitinase-like domain containing TgCLP1 is partially present in the bradyzoite microneme and confirmed, albeit partially, its previous identification in the tachyzoite microneme. Furthermore, although parasites lacking TgCLP1 could convert from tachyzoites to bradyzoites and make an intact cyst wall, they failed to convert from bradyzoites to tachyzoites, indicating that TgCLP1 is necessary for bradyzoite reactivation. Taken together, our findings deepen our understanding of the molecular basis of recrudescence and could contribute to the development of novel strategies for the control of toxoplasmosis.

Immunoglobulin G4-related Disease with Multiple Organs Involvement Depicted on FDG PET/CT: A Case Report and Literature Review.

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is a relatively rare immune-mediated chronic inflammatory disease with fibrosis newly defined in recent years. It can involve multiple systems and organs with complex clinical manifestations. Due to mass-like lesions, it is easily misdiagnosed as tumors. CASE REPORT: Herein, we report a 57-year-old woman treated for submandibular mass and anosmia. The serum IgG4 level was increased. The biopsy of the submandibular gland indicated salivary gland tissue and hyperplasia of fibrous tissue and lymphoid tissue. Immunohistochemical examination showed a large number of IgG4-positive plasma cells. M protein was found in the patient's serum by immunofixation electrophoresis, and plasma cell diseases were excluded by bone marrow puncture. PET/CT examination showed that besides the submandibular glands, the parotid gland, common bile duct, the transitional part of the left renal pelvis and ureter, retroperitoneum in the lower abdomen, and multiple lymph nodes were also involved. The patient was diagnosed with IgG4-RD, and after treatment with glucocorticoid, the enlargement of submandibular glands and decreased olfactory function improved. After 14 weeks of treatment, the serological examinations, PET/CT, and ultrasound re-examination results showed significant improvement. So far, the patient has been followed up for 27 months and is in continuous remission. CONCLUSION: This case report aims to raise awareness of IgG4-RD and explore the value of PET/CT in the diagnosis and efficacy monitoring of the disease.

Plasma exchange for anti-MDA5 antibody-positive dermatomyositis-associated rapidly progressive interstitial lung disease: A case report and literature review.

The prognosis of anti-MDA5-positive dermatomyositis (DM)-associated rapidly progressive interstitial lung disease (RPILD) is extremely poor and effective treatment options are limited. In addition, the risk of infection during immunosuppressive treatment is a major challenge. We report here, a case of RPILD in a 31-year-old man with anti-MDA5 antibody-positive DM. Despite treatment with methylprednisolone and human immunoglobulin, his lung condition worsened and his serum ferritin levels increased. Six cycles of plasma exchange (PE) adjuvant treatment significantly mitigated his symptoms and he was discharged from hospital two months later. We suggest that PE may be a promising therapeutic option for patients with anti-MDA5-positive DM-associated RPILD. However, randomized, controlled studies are required to confirm our findings.

Metastasis-associated lung adenocarcinoma transcript 1 induces methyl-CpG-binding domain protein 4 in mice with recurrent spontaneous abortion caused by anti-phospholipid antibody positivity.

INTRODUCTION: Antiphospholipid syndrome is an autoimmune disease characterized by pregnancy-related morbidity, related to persistent positivity of antiphospholipid antibodies (APL). One of the characteristics of pregnancy-related morbidity in patients with antiphospholipid syndrome is recurrent spontaneous abortion (RSA). This study aimed to examine the mechanism through which metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) regulates methyl-CpG-binding domain protein 4 (MBD4) expression in APL-positive RSA. METHODS: Clinical samples were subjected to microarray analysis to filter differentially expressed genes. RSA mice with APL positivity were generated, followed by adenoviral vector injection to artificially upregulate MALAT1. The effects of MALAT1 on the biological behavior of trophoblast cells were assessed. The downstream mechanism of MALAT1 was analyzed using subcellular fractionation and bioinformatics prediction, and the relationship between MALAT1 and CREB binding protein (CREBBP) or MBD4 was investigated in trophoblast cells. RESULTS: MALAT1 was downregulated in APL-positive RSA patients. MALAT1 was predominantly localized in the nucleus and recruited CREBBP to mediate the MBD4 transcription. In the APL-positive RSA mice overexpressing MALAT1, the expression of soluble Fms-related tyrosine kinase 1 and anticardiolipin antibody and the embryonic resorption rate were decreased, indicating that MALAT1 reduced the occurrence of RSA in mice. Moreover, MALAT1 enhanced proliferation, migration, and invasion of trophoblast cells through recruiting CREBBP to promote MBD4 expression. Silencing of CREBBP or MBD4 increased embryonic resorption rate in RSA mice overexpressing MALAT1. DISCUSSION: MALAT1 suppresses APL-positive RSA by promoting MBD4 transcription through recruitment of CREBBP to the MBD4 promoter region.

MDA5 expression is associated with TGF-ß-induced fibrosis: potential mechanism of interstitial lung disease in anti-MDA5 dermatomyositis.

OBJECTIVES: This study aimed to investigate the high-resolution CT (HRCT) characteristics of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5 DM-ILD), and to clarify the underlying mechanisms of the clinical phenomenon. METHODS: Clinical data and HRCT patterns were compared between anti-MDA5 DM-ILD (n = 32) and antisynthetase syndrome-associated ILD (ASS-ILD) (n = 29). RNA sequencing of whole-blood samples from the two groups, and in vitro experiments using human embryonic lung fibroblasts (HELFs) were conducted to explore the potential mechanisms of the clinical findings. RESULTS: The anti-MDA5 DM-ILD subset had a significantly higher incidence of rapidly progressive ILD (RPILD) than ASS-ILD (65.6% vs 37.9%; P = 0.031). The relative percentage of the lung fibrosis HRCT pattern was significantly lower in the anti-MDA5 DM-ILD group, especially the RPILD subgroup (P = 0.013 and 0.003, respectively). RNA sequencing detected the upregulated genes including interferon-induced helicase C domain 1 (encoding MDA5), and a trend towards downregulated expression of TGF-ß signalling components in anti-MDA5 DM-ILD. In vitro culture of HELFs revealed that upregulated expression of MDA5 in HELFs was correlated with the downregulated expression of alpha smooth muscle actin, connective tissue growth factor, collagen I and collagen III by suppressing the TGF-ß signalling pathway. CONCLUSIONS: Anti-MDA5 DM-ILD patients have significantly less lung fibrosis and elevated MDA5 expression. The upregulated expression of MDA5 has relations with the suppression of the pro-fibrotic function of fibroblasts via the TGF-ß signalling pathway, which may partially explain the mechanism of the clinical phenomenon.

The relationship between JAK2(V617F) mutation and dermatomyositis-a case report and literature review.

The JAK family (JAK1, JAK2, JAK3, and TYK2) have recently emerged as a potential therapeutic management in controlling severe and refractory dermatomyositis. Meanwhile, the progress in the discovery of JAK blockers is significant, with an increasing number of selective JAK inhibitors reported and some are in or prepare for clinical trials. However, the importance of each JAK in dermatomyositis is unclear, which is critical for a comprehensive understanding of dermatomyositis and significant for forming mechanism-based strategy. Here, we presented a case with clinically amyopathic dermatomyositis and essential thrombocytosis with a somatic constitutive active mutation of JAK2(V617F). The coexistence of these two uncommon diseases attracted us to investigate their underlying relationship. To this end, we characterized the clinical course and laboratory findings of this patient. Particularly, we correlated JAK2(V617F) mutation burden in affected peripheral blood subset with clinical activity score of dermatomyositis. Based on our observation, we concluded that these two diseases are independent disorders, and JAK2(V617F) mutation burden is irrelevant to the severity of dermatomyositis. Finally, we reviewed the literature and summarized them with a thorough discussion.

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus.

Dysregulated B-cell activation plays pivotal roles in systemic lupus erythematosus (SLE), which makes B-cell depletion a potential strategy for SLE treatment. The clinical success of anti-CD19 CAR-T cells in treating B-cell malignancies has attracted the attention of researchers. In this study, we aimed to investigate the feasibility of applying anti-CD19 CAR-T cell therapy to SLE treatment in a mouse disease model. We constructed murine anti-CD19 CARs with either CD28 or 4-1BB as the intracellular costimulatory motif and evaluated the therapeutic function of the corresponding CAR-T cells by infusing them into MRL-lpr mice. Furthermore, anti-CD19 CAR-T cells were transferred to MRL-lpr mice before the onset of disease to determine their role in SLE prevention. According to our observations, compared with antibody treatment, the adoptive transfer of our anti-CD19 CAR-T cells showed a more sustained B-cell-depletion effect in MRL-lpr mice. The transfer of syngeneic anti-CD19 CAR-T cells not only prevented disease pathogenesis before the onset of disease symptoms but also displayed therapeutic benefits at a later stage after disease progression. We also tried to optimize the treatment strategy and found that compared with CAR-T cells with the CD28 costimulatory motif, CAR-T cells with the 4-1BB costimulatory motif showed better therapeutic efficiency without cell enrichment. Taken together, these results show that anti-CD19 CAR-T cell therapy was effective in the prevention and treatment of a murine model of SLE, indicating its potential for clinical use in patients.

Immunoglobulin G4-related sclerosing cholangitis mimicking cholangiocarcinoma: a case report and literature review.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a novel clinical disease that is characterized by elevated serum IgG4 concentrations and tumefaction or tissue infiltrated by IgG4+ plasma cells. The clinical manifestations of IgG4-RD depend on the type of tissues affected. IgG4-related sclerosing cholangitis is a type of IgG4-RD. We report a patient who initially visited a local hospital with a 5-month history of jaundice. He was found to have a mass in the upper part of the common bile duct that mimicked cholangiocarcinoma. He underwent surgery in our hospital and was later diagnosed with IgG4-related sclerosing cholangitis. We administered prednisolone 40 mg once a day for treatment. Taking into account the possible side effects of moderate-dose hormone therapy, we also administered teprenone, potassium chloride, and calcium carbonate. The patient did not have any recurrence of symptoms or adverse drug reactions during follow-up.

Screening of compound libraries for inhibitors of Toxoplasma growth and invasion.

Toxoplasma gondii can infect virtually all warm-blooded animals, including humans. It can differentiate between rapidly replicating tachyzoites that cause acute infection and slowly growing bradyzoites in tissue cysts. Treatment options for toxoplasmosis are challenging because current therapies cannot eradicate the latent T. gondii infection that is mainly caused by the bradyzoite forms. Accordingly, recurrence of infection is a problem for immunocompromised patients and congenitally infected patients. Protein kinases have been widely studied in eukaryotic cells, and while little is known about signaling in Toxoplasma infection, it is likely that protein kinases play a key role in parasite proliferation, differentiation, and probably invasion. To identify optimized new kinase inhibitors for drug development against T. gondii, we screened a library of kinase inhibitor compounds for anti-Toxoplasma activity and host cell cytotoxicity. Pyrimethamine served as a positive control and 0.5% DMSO was used as a negative control. Among the 80 compounds screened, 6 compounds demonstrated ≥ 80% parasite growth inhibition at concentrations at which 5 compounds did not suppress host cell viability, while 3 kinase inhibitors (Bay 11-7082, Tyrphostin AG 1295 and PD-98059) had suppressive effects individually on parasite growth and host cell invasion, but did not strongly induce bradyzoite formation.

Nanoparticles show potential to retard bradyzoites in vitro formation of Toxoplasma gondii.

Toxoplasmosis is a common parasitic disease caused by Toxoplasma gondii (Nicolle et Manceaux, 1908), an obligate parasite capable of infecting a range of cell types in almost all warm-blooded animals. Upon infecting an intermediate host, the parasites differentiate into tachyzoites which rapidly infect host tissues. Usually, the invading parasites are cleared by the immune system and administered drugs, but some tachyzoites differentiate into bradyzoites forming tissue cysts. These tissue cysts could serve as a source for re-infection and exacerbations. Currently, treatment for toxoplasmosis is limited and, moreover, there are no drugs for treating the cystic stage thus rendering toxoplasmosis a global burden. Recently, we demonstrated that inorganic nanoparticles showed promising activity against the tachyzoite stage T. gondii. In the present study, we evaluated nanoparticles for effect on bradyzoite formation in vitro. Data revealed that the nanoparticles limited bradyzoite burden in vitro. Further, the nanoparticles decreased the bradyzoite-specific BAG-1 promoter activity relative to the untreated control under a bradyzoite-inducing culture condition, even though this reduction in BAG-1 promoter activity waned with increasing concentrations of nanoparticles. In contrast, a parallel experiment under normal cell culture conditions showed that the nanoparticle treatment mildly increased the BAG-1 promoter activity relative to the untreated control. Taken together, the findings are evidence that nanoparticles not only possess anti-tachyzoite potential but they also have anti-bradyzoite potential in vitro.

Clinical Efficacy of Low Molecular Heparin on Unexplained Recurrent Spontaneous Abortion.

BACKGROUND: To study the clinical effect of low molecular heparin on unexplained recurrent spontaneous abortion (URSA). METHODS: A total of 120 URSA patients were collected in our hospital from October 2015 to September 2017. They were divided into two groups: control group (n = 60) and observation group (n = 60). The patients in the control group were administered with progesterone and human chorionic gonadotropin, and the observation group with low molecular heparin. Pregnancy outcomes, incidence of complications in pregnancy and adverse drug reactions were compared in the two groups. RESULTS: The pregnancy success rate of patients in the observation group (90.00%) is higher than that in the control group (68.33%) (p < 0.05). The incidence of complications in pregnancy in the observation group (90.00%) is lower than those in the control group (68.33%) (p < 0.05). The incidence of adverse drug reactions between the patients in the observation group (20.00%) and those in the control group (23.33%) showed no significant difference (p > 0.05). CONCLUSIONS: Low molecular heparin treatment can improve pregnancy success rate and reduce the incidence of complications in the URSA patients. Low molecular heparin is characterized by safety and reliability and has potential for application in clinic.

Methylprednisolone and plasmapheresis are effective for life-threatening diffuse alveolar hemorrhage and gastrointestinal hemorrhage in granulomatosis with polyangiitis: A case report and literature review.

RATIONALE: The treatment of granulomatosis with polyangiitis (GPA) with life-threatening complications, such as diffuse alveolar hemorrhage (DAH) and gastrointestinal hemorrhage (GIH), remains challenging. PATIENT CONCERNS: A 70-year-old female presented with a 6-month history of a productive cough and a 10-day history of arthralgia that progressed to respiratory failure and massive hematochezia. DIAGNOSES: Chest high-resolution computed tomography (HRCT) revealed multiple nodules, masses, and cavities. Urinalysis indicated microscopic hematuria. Test of proteinase3-anti-neutrophil cytoplasmic autoantibody (PR3-ANCA) was positive. INTERVENTIONS: The patient was transferred to the intensive care unit (ICU) and successfully treated with glucocorticoid pulse therapy and plasmapheresis. We combined mycophenolate mofetil (MMF) with glucocorticoid for maintenance treatment. OUTCOMES: The patient survived and is in a stable condition. We report this case that presented with a productive cough, followed by arthralgia, DAH, and GIH. LESSONS: Effective remission-induction therapy is a key to survival, while maintaining a balance between immunosuppression and avoiding infection is another challenge.

Interleukin-6 Deficiency Does Not Affect Motor Neuron Disease Caused by Superoxide Dismutase 1 Mutation.

BACKGROUND & AIM: Amyotrophic Lateral Sclerosis (ALS) is an adult-onset, progressive, motor neuron degenerative disease. Recent evidence indicates that inflammation is associated with many neurodegenerative diseases including ALS. Previously, abnormal levels of inflammatory cytokines including IL-1ß, IL-6 and TNF-α were described in ALS patients and/or in mouse ALS models. In addition, one study showed that blocking IL-1ß could slow down progression of ALS-like symptoms in mice. In this study, we examined a role for IL-6 in ALS, using an animal model for familial ALS. METHODS: Mice with mutant SOD1 (G93A) transgene, a model for familial ALS, were used in this study. The expression of the major inflammatory cytokines, IL-6, IL-1ß and TNF-α, in spinal cords of these SOD1 transgenic (TG) mice were assessed by real time PCR. Mice were then crossed with IL-6(-/-) mice to generate SOD1TG/IL-6(-/-) mice. SOD1 TG/IL-6(-/-) mice (n = 17) were compared with SOD1 TG/IL-6(+/-) mice (n = 18), SOD1 TG/IL-6(+/+) mice (n = 11), WT mice (n = 15), IL-6(+/-) mice (n = 5) and IL-6(-/-) mice (n = 8), with respect to neurological disease severity score, body weight and the survival. We also histologically compared the motor neuron loss in lumber spinal cords and the atrophy of hamstring muscles between these mouse groups. RESULTS: Levels of IL-6, IL-1ß and TNF-α in spinal cords of SOD1 TG mice was increased compared to WT mice. However, SOD1 TG/IL-6(-/-) mice exhibited weight loss, deterioration in motor function and shortened lifespan (167.55 ± 11.52 days), similarly to SOD1 TG /IL-6(+/+) mice (164.31±12.16 days). Motor neuron numbers and IL-1ß and TNF-α levels in spinal cords were not significantly different in SOD1 TG /IL-6(-/-) mice and SOD1 TG /IL-6 (+/+) mice. CONCLUSION: These results provide compelling preclinical evidence indicating that IL-6 does not directly contribute to motor neuron disease caused by SOD1 mutations.

Hemophagocytic syndrome secondary to adult-onset Still's disease but very similar to lymphoma.

Hemophagocytic syndrome (HPS) is a clinicopathologic entity characterized by increased proliferation and activation of benign macrophages with hemophagocytosis throughout the reticuloendothelial system. HPS may be primary, or secondary to malignancy, infections, auto-immune diseases and pharmacotherapy. In patients with adult-onset Still's disease (AOSD), HPS is a rare but life-threatening complication. Herein, we described a female patient with HPS secondary to AOSD. During the therapy, giant gastric ulcer similar to lymphoma developed after treatment with corticosteroid and nonsteroidal anti-inflammatory drugs.

Polyarthritis as a prewarning sign of occult lung cancer.

Cancer polyarthritis is an uncommon, paraneoplastic manifestation of some solid and hematological malignancies. Herein, we report the case of a 55-year-old woman who recently experienced polyarthritis for 2 months. On admission, the patient developed cough, expectoration, and fever. According to the clinical manifestations and the findings in radiological examinations and sputum cultures, pneumonia was considered. No evidence of lung cancer was noted by repeated computed tomography scan of lung, single bronchoscopy, or computed tomography-guided lung biopsy. Ultimately, the second bronchoscopy with biopsy was carried out, and lung adenocarcinoma was confirmed by pathological examination. Symptoms of polyarthritis starting 2 months before the symptoms of her lung cancer in the present case leads us to believe that polyarthritis may be a manifestation of paraneoplastic syndrome. Arthritis resolved after anticancer therapy. Our report indicates that polyarthritis of unknown cause may be suspected as a manifestation of malignancies.

The influence of excessive IL-6 production in vivo on the development and function of Foxp3+ regulatory T cells.

IL-6 is a proinflammatory cytokine and its overproduction is implicated in a variety of inflammatory disorders. Recent in vitro analyses suggest that IL-6 is a key cytokine that determines the balance between Foxp3(+) regulatory T cells (Tregs) and Th17 cells. However, it remains unclear whether excessive IL-6 production in vivo alters the development and function of Foxp3(+) Tregs. In this study, we analyzed IL-6 transgenic (Tg) mice in which serum IL-6 levels are constitutively elevated. Interestingly, in IL-6 Tg mice, whereas peripheral lymphoid organs were enlarged, and T cells exhibited activated phenotype, Tregs were not reduced but rather increased compared with wild-type mice. In addition, Tregs from Tg mice normally suppressed proliferation of naive T cells in vitro. Furthermore, Tregs cotransferred with naive CD4 T cells into SCID-IL-6 Tg mice inhibited colitis as successfully as those transferred into control SCID mice. These results indicate that overproduction of IL-6 does not inhibit development or function of Foxp3(+) Tregs in vivo. However, when naive CD4 T cells alone were transferred, Foxp3(+) Tregs retrieved from SCID-IL-6 Tg mice were reduced compared with SCID mice. Moreover, the Helios(-) subpopulation of Foxp3(+) Tregs, recently defined as extrathymic Tregs, was significantly reduced in IL-6 Tg mice compared with wild-type mice. Collectively, these results suggest that IL-6 overproduced in vivo inhibits inducible Treg generation from naive T cells, but does not affect the development and function of natural Tregs.

[The clinical and pathological characteristics of histiocytic necrotizing lymphadenitis: analysis of 52 cases].

OBJECTIVE: To study the clinical manifestation and pathological features of histiocytic necrotizing lymphadenitis (Kikuchi's disease, KD). METHODS: 52 patients with KD were collected to analyze the clinical manifestation, pathological features of biopsy lymph nodes, diagnosis and treatment. RESULTS: 41 cases (79%) were female of the 52 patients. The main clinical features included persistent fever (100%), single (23%)/multi (77%)-lymphadenopathy (always in cervical region), pleomorphism erythra (35%), neutropenia (76%), elevated erythrocyte sedimentation rate (100%), insensitivity to antibiotics (100%) and sensitivity to small dosage glucocorticoid (81%). 26 cases (50%) had elevated aspartate aminotransferase and/or alanine aminotransferase, but only 7 cases (13%) had upper respiratory tract symptom like influenza. Pathological features included distinctive necrosis, loss of lymph node structure, infiltration with histiocytes and lymphocytes, absence of neutrophils. Immunohistochemical stainings showed CD(68) positive for histiocytes and CD(3), CD(45) RO positive for T lymphocytes. CONCLUSION: Diagnosis of KD relies on the pathological examination and immunohistochemical staining.