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Melanoma differentiation-associated gene 5 amyopathic dermatomyositis following an acute Mycoplasma pneumoniae infection: a case report [Case Report]

Hoey, Jessica; Solomon, Jenny Lue; Kim, Brandon; Carsons, Steven; Nusbaum, Julie
BACKGROUND:A previously healthy young male of Southeast Asian descent presented with 6 weeks of fevers, cough, mucocutaneous ulcers, arthritis, and myalgias. Initial workup revealed positive Mycoplasma pneumoniae immunoglobulin M, and the patient was treated with antibiotics without relief of symptoms. Rheumatologic workup revealed highly positive melanoma differentiation-associated gene 5 antibody. Viral infections are thought to potentially trigger loss of self tolerance, and prompt the autoimmunity cascade that can result in conditions such as dermatomyositis. To our knowledge, this is the first case report demonstrating a non-viral infection, specifically Mycoplasma pneumoniae, as the inciting infectious trigger for the anti-melanoma differentiation-associated gene 5 dermatomyositis subtype. CASE PRESENTATION/METHODS:A 20-year-old southeast Asian-American male with no significant past medical history presented with symptoms of intermittent fevers, nonproductive cough, dry eyes, oral ulcers, rash, arthritis, and myalgias. The patient was noted to have erythematous papules across the bilateral hands along the lateral digits and palms, as well as synovitis involving the bilateral hands and feet. Immunoglobulin M antibodies were positive for Mycoplasma pneumoniae. The patient was diagnosed with mycoplasma pneumonia. The patient did not respond to a course of antibiotics, leading to rheumatological testing that found highly positive melanoma differentiation-associated gene 5 autoantibody. Muscle enzyme and electromyography testing were normal, indicating clinically amyopathic disease. Methylprednisolone was initiated, with resolution of fevers and improvement of arthritis and myalgias. The cutaneous lesions on the digits and palms improved. CONCLUSIONS:This patient presented with symptoms of fever, cough, oral ulcers, rashes, and arthritis, and blood work demonstrated the presence of immunoglobulin M antibodies to Mycoplasma pneumoniae. Despite antibiotic treatment for the presumed diagnosis of Mycoplasma pneumoniae infection, the patient did not improve, prompting rheumatological workup and revealing melanoma differentiation-associated gene 5 autoantibodies. This case suggests that infections, other than viral, can trigger the autoinflammatory cascade, leading to the development of amyopathic melanoma differentiation-associated gene 5 dermatomyositis.
PMID: 36316755
ISSN: 1752-1947
CID: 5358232

Hydroxychloroquine Effects on THP-1 Macrophage Cholesterol Handling: Cell Culture Studies Corresponding to the TARGET Cardiovascular Trial

Ahmed, Saba; Konig, Justin; Kasselman, Lora J; Renna, Heather A; De Leon, Joshua; Carsons, Steven E; Reiss, Allison B
PMID: 36143964
ISSN: 1648-9144
CID: 5333202

Cognitive changes mediated by adenosine receptor blockade in a resveratrol-treated atherosclerosis-prone lupus mouse model

Kasselman, Lora J; Renna, Heather A; Voloshyna, Iryna; Pinkhasov, Aaron; Gomolin, Irving H; Teboul, Isaac; De Leon, Joshua; Carsons, Steven E; Reiss, Allison B
Background and aim/UNASSIGNED:Resveratrol is a bioactive molecule used in dietary supplements and herbal medicines and consumed worldwide. Prior work showed that resveratrol's anti-atherogenic properties are mediated in part through the adenosine A2A receptor. The present study explores the potential contribution of adenosine A2A receptor activation to neuroprotective action of resveratrol on cognitive deficits in a model of atherosclerosis-prone systemic lupus erythematosus. Experimental procedure/UNASSIGNED:Using behavioral analysis (open field, static rod, novel object recognition) and QRT-PCR, this study measured working memory, anxiety, motor coordination, and expression of mRNA in the brain. Results and conclusion/UNASSIGNED:Data indicate that resveratrol increases working memory, on average but not statistically, and shows a trend towards improved motor coordination (p = 0.07) in atherosclerosis-prone lupus mice. Additionally, resveratrol tends to increase mRNA levels of SIRT1, decrease vascular endothelial growth factor and CX3CL1 mRNA in the hippocampus. Istradefylline, an adenosine A2A receptor antagonist, antagonizes the effects of resveratrol on working memory (p = 0.04) and the expression of SIRT1 (p = 0.03), vascular endothelial growth factor (p = 0.04), and CX3CL1 (p = 0.03) in the hippocampus.This study demonstrates that resveratrol could potentially be a therapeutic candidate in the modulation of cognitive dysfunction in neuropsychiatric lupus, especially motor incoordination. Further human studies, as well as optimization of resveratrol administration, could confirm whether resveratrol may be an additional resource available to reduce the burden of cognitive impairment associated with lupus. Additionally, further studies need to address the role of A2A blockade in cognitive function among the autoimmune population. Section/UNASSIGNED:3. Dietary therapy/nutrients supplements. Taxonomy classification by EVISE/UNASSIGNED:autoimmunity, inflammation, neurology.
PMID: 36081818
ISSN: 2225-4110
CID: 5337222

Methotrexate effects on adenosine receptor expression in peripheral monocytes of persons with type 2 diabetes and cardiovascular disease

Reiss, Allison Bethanne; Teboul, Isaac; Kasselman, Lora; Ahmed, Saba; Carsons, Steven E; De Leon, Joshua
The Cardiovascular Inflammation Reduction Trial (CIRT) was designed to assess whether low-dose methotrexate (LD-MTX) would reduce future cardiac events in patients with metabolic syndrome or type 2 diabetes (T2DM) who are post-myocardial infarction (MI) or have multivessel disease. Our previous work indicates that MTX confers atheroprotection via adenosine A2A receptor (A2AR) activation. In order for A2AR ligation to reduce cardiovascular events, A2AR levels would need to be preserved during MTX treatment. This study was conducted to determine whether LD-MTX alters peripheral blood mononuclear cell (PBMC) adenosine receptor expression in persons at risk for cardiovascular events. Post-MI T2DM CIRT patients were randomized to LD-MTX or placebo (n=10/group). PBMC isolated from blood drawn at enrollment and after 6 weeks were evaluated for expression of adenosine receptors and reverse cholesterol transporters by real-time PCR. Fold change between time points was calculated using factorial analyses of variance. Compared with placebo, the LD-MTX group exhibited a trend toward an increase in A2AR (p=0.06), while A3R expression was significantly decreased (p=0.01) after 6 weeks. Cholesterol efflux gene expression did not change significantly. Persistence of A2AR combined with A3R downregulation indicates that failure of MTX to be atheroprotective in CIRT was not due to loss of adenosine receptors on PBMC ( identifier: NCT01594333).
PMID: 35606100
ISSN: 1708-8267
CID: 5283842

Characterization and outcomes of 414 patients with primary SS who developed hematological malignancies

Hernández-Molina, Gabriela; Kostov, Belchin; Brito-Zerón, Pilar; Vissink, Arjan; Mandl, Thomas; Hinrichs, Anneline C; Quartuccio, Luca; Baldini, Chiara; Seror, Raphaele; Szántó, Antonia; Isenberg, David; Gerli, Roberto; Nordmark, Gunnel; Rasmussen, Astrid; Solans-Laque, Roser; Hofauer, Benedikt; Sène, Damien; Pasoto, Sandra G; Rischmueller, Maureen; Praprotnik, Sonja; Gheita, Tamer A; Danda, Debashish; ArmaÄŸan, Berkan; Suzuki, Yasunori; Valim, Valeria; Devauchelle-Pensec, Valerie; Retamozo, Soledad; Kvarnstrom, Marika; Sebastian, Agata; Atzeni, Fabiola; Giacomelli, Roberto; Carsons, Steven E; Kwok, Seung-Ki; Nakamura, Hideki; Fernandes Moça Trevisani, Virginia; Flores-Chávez, Alejandra; Mariette, Xavier; Ramos-Casals, Manuel
OBJECTIVE:To characterize 414 patients with primary SS who developed hematological malignancies and to analyze how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. METHODS:By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Hematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. RESULTS:There were 414 patients (355 women, mean age 57 years) with hematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). 376 (91%) patients had mature B cell malignancy, nearly half MALT lymphoma (n = 197), followed by DLBCL (n = 67), nodal MZL lymphoma (n = 29), CLL/SLL (n = 19) and follicular lymphoma (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). CONCLUSION/CONCLUSIONS:In the largest reported study of hematological malignancies complicating primary SS, we confirm the overwhelming predominance of B cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.
PMID: 35385104
ISSN: 1462-0332
CID: 5219622

Treatment of Cardiovascular Disease in Rheumatoid Arthritis: A Complex Challenge with Increased Atherosclerotic Risk

Ahmed, Saba; Jacob, Benna; Carsons, Steven E; De Leon, Joshua; Reiss, Allison B
Rheumatoid arthritis (RA) carries significant risk for atherosclerotic cardiovascular disease (ASCVD). Traditional ASCVD risk factors fail to account for this accelerated atherosclerosis. Shared inflammatory pathways are fundamental in the pathogenesis of both diseases. Considering the impact of RA in increasing cardiovascular morbidity and mortality, the characterization of therapies encompassing both RA and ASCVD management merit high priority. Despite little progress, several drugs discussed here promote remission and or lower rheumatoid disease activity while simultaneously conferring some level of atheroprotection. Methotrexate, a widely used disease-modifying drug used in RA, is associated with significant reduction in cardiovascular adverse events. MTX promotes cholesterol efflux from macrophages, upregulates free radical scavenging and improves endothelial function. Likewise, the sulfonamide drug sulfasalazine positively impacts the lipid profile by increasing HDL-C, and its use in RA has been correlated with reduced risk of myocardial infraction. In the biologic class, inhibitors of TNF-α and IL-6 contribute to improvements in endothelial function and promote anti-atherogenic properties of HDL-C, respectively. The immunosuppressant hydroxychloroquine positively affects insulin sensitization and the lipid profile. While no individual therapy has elicited optimal atheroprotection, further investigation of combination therapies are ongoing.
PMID: 35056068
ISSN: 1424-8247
CID: 5131802

Influence of the age at diagnosis in the disease expression of primary Sjögren syndrome. Analysis of 12,753 patients from the Sjögren Big Data Consortium

Retamozo, Soledad; Acar-Denizli, Nihan; Horváth, Ildiko Fanny; Ng, Wan-Fai; Rasmussen, Astrid; Dong, Xu; Li, Xiaomei; Baldini, Chiara; Olsson, Peter; Priori, Roberta; Seror, Raphaèle; Gottenberg, Jacques-Eric; Kruize, Aike A; Hernandez-Molina, Gabriela; Vissink, Arjan; Sandhya, Pulukool; Armagan, Berkan; Quartuccio, Luca; Sebastian, Agata; Praprotnik, Sonja; Bartoloni, Elena; Kwok, Seung-Ki; Kvarnstrom, Marika; Rischmueller, Maureen; Soláns-Laqué, Roser; Sene, Damien; Pasoto, Sandra G; Suzuki, Yasunori; Isenberg, David A; Valim, Valeria; Nordmark, Gunnel; Nakamura, Hideki; Fernandes Moça Trevisani, Virginia; Hofauer, Benedikt; Sisó-Almirall, Antoni; Giacomelli, Roberto; Devauchelle-Pensec, Valerie; Bombardieri, Michele; Atzeni, Fabiola; Hammenfors, Daniel; Maure, Brenda; Carsons, Steven E; Gheita, Tamer; Sánchez-Berná, Isabel; López-Dupla, Miguel; Morel, Jacques; Inanç, Nevsun; Fonseca-Aizpuru, Eva; Morcillo, César; Vollenweider, Cristina; Melchor, Sheila; Vázquez, Marcos; Díaz-Cuiza, Ericka; Consani-Fernández, Sandra; de-Miguel-Campo, Borja; Szántó, Antónia; Bombardieri, Stefano; Gattamelata, Angelica; Hinrichs, Anneline; Sánchez-Guerrero, Jorge; Danda, Debashish; Kilic, Levent; De Vita, Salvatore; Wiland, Piotr; Gerli, Roberto; Park, Sung-Hwan; Wahren-Herlenius, Marie; Bootsma, Hendrika; Mariette, Xavier; Ramos-Casals, Manuel; Brito-Zerón, Pilar
OBJECTIVES/OBJECTIVE:To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjögren's syndrome (pSS). METHODS:By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression. RESULTS:There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R2 0.87) and the frequency of abnormal oral tests (adjusted R2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase). CONCLUSIONS:The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.
PMID: 34919044
ISSN: 0392-856x
CID: 5093042

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention

Reiss, Allison B; Jacob, Benna; Ahmed, Saba; Carsons, Steven E; DeLeon, Joshua
Systemic lupus erythematosus (SLE) carries a significant risk of cardiovascular disease (CVD). The prevalence of premature CVD is especially noteworthy because it occurs in premenopausal women with SLE who would otherwise have very low rates of CVD. While traditional risk factors likely play a role in development of CVD in the setting of SLE, they do not fully explain the excess risk. The pathogenesis of CVD in SLE is not fully understood, but the inflammatory nature of SLE is believed to be a key factor in accelerating atherosclerosis. Systemic inflammation may lead to an abnormal lipid profile with elevated triglycerides, total cholesterol, and low-density lipoprotein cholesterol and dysfunctional high-density lipoprotein cholesterol. Additionally, the inflammatory milieu of SLE plasma promotes endothelial dysfunction and vascular injury, early steps in the progression of atherosclerotic CVD. Despite the overall headway that has been achieved in treating lupus, innovative therapeutics specifically targeting the progression of atherosclerosis within the lupus population are currently lacking. However, there have been advancements in the development of promising modalities for diagnosis of subclinical atherosclerosis and detection of high CVD risk patients. Due to the significant impact of CVD on morbidity and mortality, research addressing prevention and treatment of CVD in SLE needs to be prioritized. This review explores the intricate interplay of SLE-specific properties that contribute to atherosclerosis and CVD within this population, as well as screening methods and possible therapies.
PMID: 33821395
ISSN: 1573-2576
CID: 4839112

Autoimmunity to Annexin A2 predicts mortality among hospitalised COVID-19 patients [Letter]

Zuniga, Marisol; Gomes, Claudia; Carsons, Steven E; Bender, Michael T; Cotzia, Paolo; Miao, Qing Robert; Lee, David C; Rodriguez, Ana
PMID: 34244321
ISSN: 1399-3003
CID: 4938032

Response [Letter]

Lee, Augustine S; Scofield, R Hal; Hammitt, Katherine Morland; Carsons, Steven E; Carteron, Nancy L
PMID: 34488985
ISSN: 1931-3543
CID: 5011392