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Article ; Online: Serum stimulation of CCR7 chemotaxis due to coagulation factor XIIa-dependent production of high-molecular-weight kininogen domain 5.

Ponda, Manish P / Breslow, Jan L

Proceedings of the National Academy of Sciences of the United States of America

2016 Volume 113, Issue 45, Page(s) E7059–E7068

Abstract: Chemokines and their receptors play a critical role in immune function by directing cell-specific movement. C-C chemokine receptor 7 (CCR7) facilitates entry of T cells into lymph nodes. CCR7-dependent chemotaxis requires either of the cognate ligands C- ... ...

Abstract	Chemokines and their receptors play a critical role in immune function by directing cell-specific movement. C-C chemokine receptor 7 (CCR7) facilitates entry of T cells into lymph nodes. CCR7-dependent chemotaxis requires either of the cognate ligands C-C chemokine ligand 19 (CCL19) or CCL21. Although CCR7-dependent chemotaxis can be augmented through receptor up-regulation or by increased chemokine concentrations, we found that chemotaxis is also markedly enhanced by serum in vitro. Upon purification, the serum cofactor activity was ascribed to domain 5 of high-molecular-weight kininogen. This peptide was necessary and sufficient for accelerated chemotaxis. The cofactor activity in serum was dependent on coagulation factor XIIa, a serine protease known to induce cleavage of high-molecular-weight kininogen (HK) at sites of inflammation. Within domain 5, we synthesized a 24-amino acid peptide that could recapitulate the activity of intact serum through a mechanism distinct from up-regulating CCR7 expression or promoting chemokine binding to CCR7. This peptide interacts with the extracellular matrix protein thrombospondin 4 (TSP4), and antibodies to TSP4 neutralize its activity. In vivo, an HK domain 5 peptide stimulated homing of both T and B cells to lymph nodes. A circulating cofactor that is activated at inflammatory foci to enhance lymphocyte chemotaxis represents a powerful mechanism coupling inflammation to adaptive immunity.
Language	English
Publishing date	2016-10-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1615671113
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Article ; Online: The association of triglyceride levels with the incidence of initial and recurrent acute pancreatitis.

Sanchez, Robert J / Ge, Wenzhen / Wei, Wenhui / Ponda, Manish P / Rosenson, Robert S

Lipids in health and disease

2021 Volume 20, Issue 1, Page(s) 72

Abstract: Background: This retrospective cohort study assessed the annualized incidence rate (IR) of acute pancreatitis (AP) in a nationally representative US adult population, as well as the variation in the risk of AP events across strata of triglyceride (TG) ... ...

Abstract	Background: This retrospective cohort study assessed the annualized incidence rate (IR) of acute pancreatitis (AP) in a nationally representative US adult population, as well as the variation in the risk of AP events across strata of triglyceride (TG) levels. Methods: Data were obtained from IQVIA's US Ambulatory Electronic Medical Records (EMR) database linked with its LRxDx Open Claims database. Inclusion criteria included ≥1 serum TG value during the overlapping study period of the EMR and claims databases, ≥1 claim in the 12-month baseline period, and ≥ 1 claim in the 12 months post index. All TG measurements were assigned to the highest category reached: < 2.26, ≥2.26 to ≤5.65, > 5.65 to ≤9.94, > 9.94, and > 11.29 mmol/L (< 200, ≥200 to ≤500, > 500 to ≤880, > 880, and > 1000 mg/dL, respectively). The outcome of interest was AP, defined as a hospitalization event with AP as the principal diagnosis. Results: In total, 7,119,195 patients met the inclusion/exclusion criteria, of whom 4158 (0.058%) had ≥1 AP events in the prior 12 months. Most patients (83%) had TGs < 2.26 mmol/L (< 200 mg/dL), while < 1% had TGs > 9.94 mmol/L (> 880 mg/dL). Overall, the IR of AP was low (0.08%; 95% confidence internal [CI], 0.08-0.08%), but increased with increasing TGs (0.08% in TGs < 2.26 mmol/L [< 200 mg/dL] to 1.21% in TGs > 11.29 mmol/L [> 1000 mg/dL]). In patients with a prior history of AP, the IR of AP increased dramatically; patients with ≥2 AP events at baseline had an IR of 29.98% (95% CI, 25.1-34.9%). Conclusion: The risk of AP increases with increasing TG strata; however, the risk increases dramatically among patients with a recent history of AP.
MeSH term(s)	Female ; Humans ; Hypertriglyceridemia/blood ; Hypertriglyceridemia/complications ; Incidence ; Male ; Middle Aged ; Pancreatitis/blood ; Pancreatitis/epidemiology ; Pancreatitis/etiology ; Recurrence ; Retrospective Studies ; Risk Factors ; Triglycerides/blood
Chemical Substances	Triglycerides
Language	English
Publishing date	2021-07-18
Publishing country	England
Document type	Journal Article
ISSN	1476-511X
ISSN (online)	1476-511X
DOI	10.1186/s12944-021-01488-8
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Article: Use of Janus kinase inhibitors in dermatomyositis: a systematic literature review.

Paik, Julie J / Lubin, Greg / Gromatzky, Austin / Mudd, Paul N / Ponda, Manish P / Christopher-Stine, Lisa

Clinical and experimental rheumatology

2022 Volume 41, Issue 2, Page(s) 348–358

Abstract: Dermatomyositis (DM) is an idiopathic inflammatory myopathy that commonly manifests with proximal muscle weakness and is associated with extramuscular pathology, including characteristic skin lesions such as Gottron's papules and heliotrope rash, as well ...

Abstract	Dermatomyositis (DM) is an idiopathic inflammatory myopathy that commonly manifests with proximal muscle weakness and is associated with extramuscular pathology, including characteristic skin lesions such as Gottron's papules and heliotrope rash, as well as lung, gastrointestinal, joint, and cardiac involvement. Systemic corticosteroids are a cornerstone of therapy, and more recently intravenous immunoglobulin (IVIG; OCTAGAM®) has been approved by the US Food and Drug Administration for the treatment of adults with DM. Both steroids and IVIG represent nonspecific anti-inflammatory therapy, and more targeted approaches are lacking. Transcriptomics has identified upregulation of interferon (IFN)-regulated genes as key features of both adult DM and juvenile DM (JDM). Accordingly, blocking IFN signalling through inhibition of the Janus kinase (JAK) pathway represents a potential treatment option for DM. Placebo-controlled trial data assessing the use of JAK inhibitors for the treatment of DM are limited; as such, a systematic literature review was undertaken to assess the evidence of JAK inhibitors in the treatment of patients with DM. Terms related to DM and JAK inhibitors were searched using PubMed, Embase, Web of Science, Scopus, and Dimensions to identify peer-reviewed publications reporting patients with DM who were treated with a JAK inhibitor. Baseline demographics, clinical characteristics, and treatment outcome data were extracted. A total of 48 publications reporting 145 unique patients (adult DM, n=84; JDM, n=61) were identified. Among cases of adult DM, 61 of 84 (73%) had refractory skin disease at baseline, and all (61 of 61) reported improvement in cutaneous symptoms. Of patients with adult DM, 16 of 84 (19%) had refractory muscle disease at baseline, and all (16 of 16) reported improvement in muscle symptoms. In patients with adult DM complicated by interstitial lung disease (ILD; n=33), 31 (94%) patients improved with JAK inhibitor treatment. Among cases of JDM with refractory skin disease at baseline (60 of 61), most patients (57 of 60; 95%) showed improvements in skin symptoms after JAK inhibitor treatment. Of patients with JDM with refractory muscle disease at baseline (36 of 61), most (30 of 36; 83%) reported improvement in muscle symptoms. Four patients with JDM and ILD experienced improvement in lung disease activity following treatment with a JAK inhibitor. Among both DM and JDM cases, all patients (17 with DM and 16 with JDM) who had elevated serum IFN and/or IFN-stimulated gene expression at baseline showed reduction in IFN or IFN gene expression. Although the conclusions that can be drawn from this analysis are limited because of the differences in assessments used across publications, overall treatment of patients with DM or JDM with a JAK inhibitor was associated with significant improvement of a wide range of DM manifestations, including skin lesions, muscle weakness, and ILD. Our systematic literature review suggests that JAK inhibitors may be a viable treatment option for DM/JDM, and randomised controlled trials are necessary to confirm these findings.
MeSH term(s)	Adult ; Humans ; Dermatomyositis/complications ; Janus Kinase Inhibitors/therapeutic use ; Immunoglobulins, Intravenous/therapeutic use ; Muscular Diseases ; Muscle Weakness/complications ; Lung Diseases, Interstitial/complications
Chemical Substances	Janus Kinase Inhibitors ; Immunoglobulins, Intravenous
Language	English
Publishing date	2022-06-28
Publishing country	Italy
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	605886-3
ISSN	1593-098X ; 0392-856X
ISSN (online)	1593-098X
ISSN	0392-856X
DOI	10.55563/clinexprheumatol/hxin6o
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Article ; Online: Are we overinterpreting serum vitamin D data?

Holt, Peter R / Ponda, Manish P

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2014 Volume 12, Issue 9, Page(s) 1578–1579

MeSH term(s)	Diverticulitis/epidemiology ; Female ; Humans ; Male ; Vitamin D/blood
Chemical Substances	Vitamin D (1406-16-2)
Language	English
Publishing date	2014-09
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2013.12.029
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Zs.A 5836: Show issues

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Article ; Online: Quantifying Human Monocyte Chemotaxis In Vitro and Murine Lymphocyte Trafficking In Vivo.

Prangley, Eliza / Kumar, Terrence / Ponda, Manish P

Journal of visualized experiments : JoVE

2017 , Issue 128

Abstract: Chemotaxis is migration along a specific chemical ... ...

Abstract	Chemotaxis is migration along a specific chemical gradient
MeSH term(s)	Animals ; Chemotaxis, Leukocyte/physiology ; Flow Cytometry/methods ; Lymphocytes/cytology ; Lymphocytes/metabolism ; Lymphocytes/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Monocytes/cytology
Language	English
Publishing date	2017-10-30
Publishing country	United States
Document type	Journal Article ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/56218
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Article ; Online: Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial.

Rosenson, Robert S / Gaudet, Daniel / Ballantyne, Christie M / Baum, Seth J / Bergeron, Jean / Kershaw, Erin E / Moriarty, Patrick M / Rubba, Paolo / Whitcomb, David C / Banerjee, Poulabi / Gewitz, Andrew / Gonzaga-Jauregui, Claudia / McGinniss, Jennifer / Ponda, Manish P / Pordy, Robert / Zhao, Jian / Rader, Daniel J

Nature medicine

2023 Volume 29, Issue 3, Page(s) 729–737

Abstract: ... syndrome without LPL pathway mutations (n = 19). Fifty-one patients (males, n = 27; females, n = 24 ...

Abstract	Severe hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis. Current therapeutic approaches for sHTG are often insufficient to reduce triglycerides and prevent acute pancreatitis. This phase 2 trial ( NCT03452228 ) evaluated evinacumab (angiopoietin-like 3 inhibitor) in three cohorts of patients with sHTG: cohort 1, familial chylomicronemia syndrome with bi-allelic loss-of-function lipoprotein lipase (LPL) pathway mutations (n = 17); cohort 2, multifactorial chylomicronemia syndrome with heterozygous loss-of-function LPL pathway mutations (n = 15); and cohort 3, multifactorial chylomicronemia syndrome without LPL pathway mutations (n = 19). Fifty-one patients (males, n = 27; females, n = 24) with a history of hospitalization for acute pancreatitis were randomized 2:1 to intravenous evinacumab 15 mg kg
MeSH term(s)	Male ; Female ; Humans ; Lipoprotein Lipase/genetics ; Acute Disease ; Single-Blind Method ; Pancreatitis/drug therapy ; Pancreatitis/genetics ; Hypertriglyceridemia/drug therapy ; Hypertriglyceridemia/genetics ; Hyperlipoproteinemia Type I/drug therapy ; Hyperlipoproteinemia Type I/genetics ; Triglycerides ; Mutation/genetics
Chemical Substances	Lipoprotein Lipase (EC 3.1.1.34) ; evinacumab (T8B2ORP1DW) ; Triglycerides
Language	English
Publishing date	2023-03-06
Publishing country	United States
Document type	Randomized Controlled Trial ; Clinical Trial, Phase II ; Journal Article
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-023-02222-w
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 39: Show issues

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Article ; Online: Vitamin D3 repletion in chronic kidney disease stage 3: effects on blood endotoxin activity, inflammatory cytokines, and intestinal permeability.

Ponda, Manish P / Breslow, Jan L

Renal failure

2013 Volume 35, Issue 4, Page(s) 497–503

Abstract: ... levels (r = -0.60, p = 0.04). Endotoxin activity decreased by 25% from baseline (p = 0.03). Despite ...

Abstract	Background: Vitamin D deficiency is common in the general population and even more prevalent in patients with chronic kidney disease (CKD). Low 25-hydroxyvitamin D [25(OH)D] levels have been associated with cardiovascular disease, though a definitive mechanistic link has not been established. Further, it is unclear if repleting vitamin D mitigates the excess risk observed in epidemiologic studies. Because vitamin D may regulate innate immunity and gut epithelial differentiation, we hypothesized that oral cholecalciferol (D3) would result in decreased blood endotoxin activity, a potential risk factor for cardiovascular disease. STUDY DESIGN, SETTING & PARTICIPANTS, INTERVENTION: We studied 12 stable outpatients with CKD stage 3 and 25(OH)D deficiency, who received D3 30,000 units weekly for 8 weeks. The primary endpoint was the change in blood endotoxin activity. Results: Baseline endotoxin activity correlated with 25(OH)D levels (r = -0.60, p = 0.04). Endotoxin activity decreased by 25% from baseline (p = 0.03). Despite the decrease in endotoxin activity, there was no change in intestinal permeability. Conclusion: The results of this study suggest that vitamin D repletion therapy may have an effect on endotoxin activity in early CKD. Further intervention studies using vitamin D in the CKD population are required.
MeSH term(s)	Aged ; Biomarkers/blood ; Cholecalciferol/administration & dosage ; Cytokines/blood ; Endotoxins/blood ; Female ; Humans ; Inflammation/blood ; Intestinal Mucosa/metabolism ; Intestines/physiopathology ; Male ; Middle Aged ; Permeability ; Renal Insufficiency, Chronic/blood ; Renal Insufficiency, Chronic/complications ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; Vitamin D Deficiency/blood
Chemical Substances	Biomarkers ; Cytokines ; Endotoxins ; Vitamin D (1406-16-2) ; Cholecalciferol (1C6V77QF41) ; 25-hydroxyvitamin D (A288AR3C9H)
Language	English
Publishing date	2013-03-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	632949-4
ISSN	1525-6049 ; 0886-022X
ISSN (online)	1525-6049
ISSN	0886-022X
DOI	10.3109/0886022X.2013.775696
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Article ; Online: Inhibition of Angiopoietin-Like Protein 3 With Evinacumab in Subjects With High and Severe Hypertriglyceridemia.

Ahmad, Zahid / Pordy, Robert / Rader, Daniel J / Gaudet, Daniel / Ali, Shazia / Gonzaga-Jauregui, Claudia / Ponda, Manish P / Shumel, Brad / Banerjee, Poulabi / Dunbar, Richard L

Journal of the American College of Cardiology

2021 Volume 78, Issue 2, Page(s) 193–195

MeSH term(s)	Angiopoietin-Like Protein 3/antagonists & inhibitors ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Humans ; Hypertriglyceridemia/blood ; Hypertriglyceridemia/drug therapy
Chemical Substances	ANGPTL3 protein, human ; Angiopoietin-Like Protein 3 ; Antibodies, Monoclonal ; evinacumab (T8B2ORP1DW)
Language	English
Publishing date	2021-07-09
Publishing country	United States
Document type	Clinical Trial, Phase I ; Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	605507-2
ISSN	1558-3597 ; 0735-1097
ISSN (online)	1558-3597
ISSN	0735-1097
DOI	10.1016/j.jacc.2021.04.091
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Zs.A 1846: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Quantifying human monocyte chemotaxis In Vitro and murine lymphocyte trafficking In Vivo

Prangley, Eliza / Kumar, Terrence / Ponda, Manish P

Journal of visualized experiments. 2017 Oct. 30, , no. 128

2017

Abstract: Chemotaxis is migration along a specific chemical gradient1. Chemokines are chemotactic cytokines that promote cellular trafficking with anatomic and temporal specificity2. Chemotaxis is a critical function of lymphocytes and other immune cells that can ... ...

Abstract	Chemotaxis is migration along a specific chemical gradient1. Chemokines are chemotactic cytokines that promote cellular trafficking with anatomic and temporal specificity2. Chemotaxis is a critical function of lymphocytes and other immune cells that can be quantitatively assessed in vitro. This manuscript describes methods that permit the evaluation of chemotaxis, both in vitro and in vivo, for diverse cell types including cell lines and native cells. The in vitro, plate-based format permits the comparison of several conditions simultaneously in real-time, and can be completed within 1-4 h. In vitro assay conditions can be manipulated to introduce agonists and antagonists, as well as differentiate chemotaxis from chemokinesis, which is random movement. For in vivo trafficking assessments, immune cells can be labeled with multiple fluorescent dyes and used for adoptive transfer. The differential labeling of cells allows for mixed cell populations to be introduced into the same animal, thereby decreasing variance and reducing the number of animals required for an adequately powered experiment. Migration into lymphoid tissue occurs in as little as 1 h, and multiple tissue compartments can be sampled. Flow cytometry following tissue harvest allows for a rapid and quantitative analysis of the migratory patterns of multiple cell types.
Keywords	agonists ; animal use reduction ; antagonists ; cell lines ; chemokines ; chemotaxis ; flow cytometry ; fluorescent dyes ; humans ; in vitro studies ; lymphocytes ; mice ; migratory behavior ; monocytes ; quantitative analysis ; variance
Language	English
Dates of publication	2017-1030
Size	p. e56218.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/56218
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Article ; Online: Component resolved diagnostics in peanut sensitized children with and without a history of clinical reaction.

Hamzavi Abedi, Yasmin / Sison, Cristina P / Ponda, Punita

Allergy and asthma proceedings

2020 Volume 41, Issue 5, Page(s) 336–340

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	2S Albumins, Plant/immunology ; Adolescent ; Antigens, Plant/immunology ; Arachis ; Child ; Child, Preschool ; Female ; Humans ; Immunization/methods ; Immunoglobulin E/blood ; Infant ; Infant, Newborn ; Male ; Medical History Taking ; Membrane Proteins/immunology ; Peanut Hypersensitivity/diagnosis ; Plant Proteins/immunology ; Reference Values ; Retrospective Studies ; Skin Tests
Chemical Substances	2S Albumins, Plant ; Antigens, Plant ; Ara h 1 protein, Arachis hypogaea ; Ara h 2 allergen, Arachis hypogaea ; Membrane Proteins ; Plant Proteins ; Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2020-08-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1312445-6
ISSN	1539-6304 ; 1088-5412
ISSN (online)	1539-6304
ISSN	1088-5412
DOI	10.2500/aap.2020.41.200061
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