Matthew Baker

All Publications

• Non-invasive Vagus Nerve Stimulation Improves Signs and Symptoms of Rheumatoid Arthritis: Results of a Pilot Study Marsal, S., Corominas, H., De Agustin De Oro, J., Perez Garcia, C., Lopez Lasanta, M., Borrell, H., Reina, D., Sanmarti, R., Javier Narvaez, F., Franco-Jarava, C., Peterfy, C., Antonio Narvaez, J., Sharma, V., Alataris, K., Genovese, M., Baker, M. WILEY. 2020

  View details for Web of Science ID 000587568506246

• CD52 Is Elevated on B cells of SLE Patients and Regulates B Cell Function. Frontiers in immunology Bhamidipati, K., Silberstein, J. L., Chaichian, Y., Baker, M. C., Lanz, T. V., Zia, A., Rasheed, Y. S., Cochran, J. R., Robinson, W. H. 2020; 11: 626820

  Abstract

  Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell dysregulation and breaks in tolerance that lead to the production of pathogenic autoantibodies. We performed single-cell RNA sequencing of B cells from healthy donors and individuals with SLE which revealed upregulated CD52 expression in SLE patients. We further demonstrate that SLE patients exhibit significantly increased levels of B cell surface CD52 expression and plasma soluble CD52, and levels of soluble CD52 positively correlate with measures of lupus disease activity. Using CD52-deficient JeKo-1 cells, we show that cells lacking surface CD52 expression are hyperresponsive to B cell receptor (BCR) signaling, suggesting an inhibitory role for the surface-bound protein. In healthy donor B cells, antigen-specific BCR-activation initiated CD52 cleavage in a phospholipase C dependent manner, significantly reducing cell surface levels. Experiments with recombinant CD52-Fc showed that soluble CD52 inhibits BCR signaling in a manner partially-dependent on Siglec-10. Moreover, incubation of unstimulated B cells with CD52-Fc resulted in the reduction of surface immunoglobulin and CXCR5. Prolonged incubation of B cells with CD52 resulted in the expansion of IgD+IgMlo anergic B cells. In summary, our findings suggest that CD52 functions as a homeostatic protein on B cells, by inhibiting responses to BCR signaling. Further, our data demonstrate that CD52 is cleaved from the B cell surface upon antigen engagement, and can suppress B cell function in an autocrine and paracrine manner. We propose that increased expression of CD52 by B cells in SLE represents a homeostatic mechanism to suppress B cell hyperactivity.

  View details for DOI 10.3389/fimmu.2020.626820

  View details for PubMedID 33658999

  View details for PubMedCentralID PMC7917337

• A Mortality Risk Score Model for Clinically Amyopathic Dermatomyositis-Associated Interstitial Lung Disease: Will It Have the Necessary "FLAIR" to Improve Clinical Outcomes? Chest Baker, M. C., Chung, L., Fiorentino, D. F. 2020; 158 (4): 1307?9

  View details for DOI 10.1016/j.chest.2020.06.001

  View details for PubMedID 33036075

• Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy. RMD open Baker, M., Chaichian, Y., Genovese, M., Derebail, V., Rao, P., Chatham, W., Bubb, M., Lim, S., Hajian, H., Gurtovaya, O., Patel, U., Tumlin, J. 2020; 6 (3)

  Abstract

  Patients with lupus membranous nephropathy (LMN) are at risk for prolonged proteinuria and progressive chronic kidney disease. There are no proven effective treatments for LMN, and controlled trials are lacking. This trial assessed the preferential Janus kinase 1 (JAK1) inhibitor filgotinib and the spleen tyrosine kinase inhibitor lanraplenib in patients with LMN.This was a phase II, randomised, double-blind trial conducted at 15 centres in the USA to evaluate the safety and efficacy of filgotinib or lanraplenib for the treatment of LMN. Eligible patients were randomised 1:1 to receive either filgotinib or lanraplenib in a blinded fashion for up to 52 weeks. The primary endpoint was the per cent change in 24-hour urine protein from baseline to week 16.Nine patients were randomised to receive filgotinib (n=5) or lanraplenib (n=4). Four patients in the filgotinib group and one patient in the lanraplenib group completed week 16. There was a median reduction of 50.7% in 24-hour urine protein after 16 weeks of treatment with filgotinib (n=4), and the median Systemic Lupus Erythematosus Disease Activity Index from the Safety of Estrogens in Lupus National Assessment score remained stable. Filgotinib treatment was well tolerated. Limited conclusions can be drawn about treatment with lanraplenib.The number of patients treated in this study was small, and only limited conclusions can be drawn. There may be a therapeutic benefit with filgotinib treatment, which may support future investigations with filgotinib or other JAK inhibitors in patients with LMN.NCT03285711.

  View details for DOI 10.1136/rmdopen-2020-001490

  View details for PubMedID 33380521

• Osteoarthritis risk is reduced after treatment with ticagrelor compared to clopidogrel: a propensity score matching analysis. Arthritis & rheumatology (Hoboken, N.J.) Baker, M. C., Weng, Y., William, R. H., Ahuja, N., Rohatgi, N. 2020

  Abstract

  Osteoarthritis (OA) is a common cause of joint pain and disability, and effective treatments are lacking. Extracellular adenosine has anti-inflammatory effects and can prevent and treat OA in animal models. Ticagrelor and clopidogrel are both used in patients with coronary artery disease, but only ticagrelor increases extracellular adenosine. The aim of this study was to determine whether treatment with ticagrelor was associated with a lower risk of OA.We conducted a 1:2 propensity score matching analysis using the Optum Clinformatics? Data Mart from 2011 to 2017. We included patients who received either ticagrelor or clopidogrel for at least 90 days and excluded those with a prior diagnosis of OA or inflammatory arthritis. OA was identified using International Classification of Diseases codes. The primary outcome was the time to diagnosis of OA after treatment with ticagrelor versus clopidogrel.Our propensity score matched cohort consisted of 7,007 ticagrelor-treated patients and 14,014 clopidogrel-treated patients, with a median number of days on treatment of 287 and 284 respectively. For both groups, the mean age was 64 years, and 73% of the patients were male. Multivariate Cox-regression analysis estimated a hazard ratio of 0.71 (95% CI 0.64-0.79, p<0.001) for developing OA after treatment with ticagrelor compared to clopidogrel.Treatment with ticagrelor was associated with a 29% lower risk of developing OA compared to clopidogrel over five years of follow-up. We hypothesize that the reduction in OA seen in patients who received ticagrelor may in part be due to increased extracellular adenosine.

  View details for DOI 10.1002/art.41412

  View details for PubMedID 32564514

• Dermatomyositis Associated With a Skull Base Chondrosarcoma JCR-JOURNAL OF CLINICAL RHEUMATOLOGY Baker, M. C., Smith, G. P., Miloslavsky, E. M. 2019; 25 (4): E50?E53

  View details for DOI 10.1097/RHU.0000000000000732

  View details for Web of Science ID 000470908400009

• TNF-alpha inhibition for the treatment of cardiac sarcoidosis. Seminars in arthritis and rheumatism Baker, M. C., Sheth, K., Witteles, R., Genovese, M. C., Shoor, S., Simard, J. F. 2019

  Abstract

  Tumor necrosis factor alpha (TNF-?) inhibitors are increasingly being used for treating refractory cardiac sarcoidosis. There is a theoretical risk, however, that these therapies can worsen heart failure, and reports on efficacy and safety are lacking.We conducted a retrospective review of all cardiac sarcoidosis patients seen at Stanford University from 2009 to 2018. Data were collected on patient demographics, diagnostic testing, and treatment outcomes.We identified 77 cardiac sarcoidosis patients, of which 20 (26%) received TNF-? inhibitor treatment. The majority were treated for progressive heart failure or tachyarrhythmia, along with worsening imaging findings. All TNF-? inhibitor treated patients demonstrated meaningful benefit, as assessed by changes in advanced imaging, echocardiographic measures of cardiac function, and prednisone use.A large cohort (n = 77) of cardiac sarcoidosis patients has been treated at Stanford University. Roughly one-fourth of these patients (n = 20) received TNF-? inhibitors. Of these patients, none had worsening heart failure and all saw clinical benefit. These results help support the use of TNF-? inhibitors for the treatment of cardiac sarcoidosis based on real-world evidence and highlight the need for future prospective studies.

  View details for DOI 10.1016/j.semarthrit.2019.11.004

  View details for PubMedID 31806154

• Security and Privacy Qualities of Medical Devices: An Analysis of FDA Postmarket Surveillance PLOS ONE Kramer, D. B., Baker, M., Ransford, B., Molina-Markham, A., Stewart, Q., Fu, K., Reynolds, M. R. 2012; 7 (7)

  Abstract

  Medical devices increasingly depend on computing functions such as wireless communication and Internet connectivity for software-based control of therapies and network-based transmission of patients' stored medical information. These computing capabilities introduce security and privacy risks, yet little is known about the prevalence of such risks within the clinical setting.We used three comprehensive, publicly available databases maintained by the Food and Drug Administration (FDA) to evaluate recalls and adverse events related to security and privacy risks of medical devices.Review of weekly enforcement reports identified 1,845 recalls; 605 (32.8%) of these included computers, 35 (1.9%) stored patient data, and 31 (1.7%) were capable of wireless communication. Searches of databases specific to recalls and adverse events identified only one event with a specific connection to security or privacy. Software-related recalls were relatively common, and most (81.8%) mentioned the possibility of upgrades, though only half of these provided specific instructions for the update mechanism.Our review of recalls and adverse events from federal government databases reveals sharp inconsistencies with databases at individual providers with respect to security and privacy risks. Recalls related to software may increase security risks because of unprotected update and correction mechanisms. To detect signals of security and privacy problems that adversely affect public health, federal postmarket surveillance strategies should rethink how to effectively and efficiently collect data on security and privacy problems in devices that increasingly depend on computing systems susceptible to malware.

  View details for DOI 10.1371/journal.pone.0040200

  View details for Web of Science ID 000306956300012

  View details for PubMedID 22829874

  View details for PubMedCentralID PMC3400651

• Enhancement of DNA tumor vaccine efficacy by gene gun-mediated codelivery of threshold amounts of plasmid-encoded helper antigen BLOOD Leitner, W. W., Baker, M. C., Berenberg, T. L., Lu, M. C., Yannie, P. J., Udey, M. C. 2009; 113 (1): 37-45

  Abstract

  Nucleic acid-based vaccines are effective in infectious disease models but have yielded disappointing results in tumor models when tumor-associated self-antigens are used. Incorporation of helper epitopes from foreign antigens into tumor vaccines might enhance the immunogenicity of DNA vaccines without increasing toxicity. However, generation of fusion constructs encoding both tumor and helper antigens may be difficult, and resulting proteins have unpredictable physical and immunologic properties. Furthermore, simultaneous production of equal amounts of highly immunogenic helper and weakly immunogenic tumor antigens in situ could favor development of responses against the helper antigen rather than the antigen of interest. We assessed the ability of 2 helper antigens (beta-galactosidase or fragment C of tetanus toxin) encoded by one plasmid to augment responses to a self-antigen (lymphoma-associated T-cell receptor) encoded by a separate plasmid after codelivery into skin by gene gun. This approach allowed adjustment of the relative ratios of helper and tumor antigen plasmids to optimize helper effects. Incorporation of threshold (minimally immunogenic) amounts of helper antigen plasmid into a DNA vaccine regimen dramatically increased T cell-dependent protective immunity initiated by plasmid-encoded tumor-associated T-cell receptor antigen. This simple strategy can easily be incorporated into future vaccine trials in experimental animals and possibly in humans.

  View details for DOI 10.1182/blood-2008-01-136267

  View details for Web of Science ID 000262162800010

  View details for PubMedID 18832136

  View details for PubMedCentralID PMC2614641