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Biglarnia, Alireza
Alternative names
Publications (10 of 36) Show all publications
Biglarnia, A.-R., Nilsson, K. E. & Nilsson, B. (2015). Complement Interception Across Humoral Incompatibility in Solid Organ Transplantation: A Clinical Perspective. In: IMMUNE RESPONSES TO BIOSURFACES: MECHANISMS AND THERAPEUTIC INTERVENTIONS. Paper presented at 1st International Conference on Immune Response to Biosurfaces, SEP 27-OCT 02, 2014, Chania, GREECE (pp. 211-233).
Open this publication in new window or tab >>Complement Interception Across Humoral Incompatibility in Solid Organ Transplantation: A Clinical Perspective
2015 (English)In: IMMUNE RESPONSES TO BIOSURFACES: MECHANISMS AND THERAPEUTIC INTERVENTIONS, 2015, p. 211-233Conference paper, Published paper (Refereed)
Abstract [en]

The humoral barrier in transplant biology is the result of preformed donor-specific antibodies (DSAs), directed either against human leukocyte antigens (HLA) or non-HLA antigens such as blood group (ABO) molecules. The term "sensitization" applies to patients carrying these antibodies. Transplantation is widely accepted as a life-saving opportunity for patients with terminal end-organ disease. However, in sensitized patients, transplant outcome is hampered by antibody-mediated rejection (AMR) as a consequence of DSA exposure. Furthermore, sensitized patients have limited access to "matched" organs from the both living and deceased donor pool. Considering the crucial role of the complement system in the pathophysiology of AMR and the availability of complement intervention therapeutics, there is a growing interest in complement-targeting strategies. This review highlights the emerging importance of monitoring and modulation of the complement system in the context of enabling transplantation across humoral incompatibility in sensitized recipients with preformed anti-HLA or natural anti-ABO antibodies. It also discusses the significance of the complement system in the induction of accommodation and further emphasizes current and future perspectives of novel complement therapeutics.

Series
Advances in Experimental Medicine and Biology, ISSN 0065-2598 ; 865
Keyword
ABO- and HLA-incompatibility, Antibody-mediated rejection, Terminal complement inhibition, Transplantation, Complement therapeutics, Desensitization
National Category
Immunology
Identifiers
urn:nbn:se:uu:diva-265645 (URN)10.1007/978-3-319-18603-0_13 (DOI)000361838300014 ()26306452 (PubMedID)978-3-319-18603-0 (ISBN)978-3-319-18602-3 (ISBN)
Conference
1st International Conference on Immune Response to Biosurfaces, SEP 27-OCT 02, 2014, Chania, GREECE
Funder
Swedish Research Council, 2013-65X-05647-34-4EU, FP7, Seventh Framework Programme, 602699
Available from: 2015-11-02 Created: 2015-11-02 Last updated: 2015-11-05Bibliographically approved
Mastellos, D. C., Yancopoulou, D., Kokkinos, P., Huber-Lang, M., Hajishengallis, G., Biglarnia, A., . . . Lambris, J. D. (2015). Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention. European Journal of Clinical Investigation, 45(4), 423-440
Open this publication in new window or tab >>Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention
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2015 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 45, no 4, p. 423-440Article, review/survey (Refereed) Published
Abstract [en]

There is a growing awareness that complement plays an integral role in human physiology and disease, transcending its traditional perception as an accessory system for pathogen clearance and opsonic cell killing. As the list of pathologies linked to dysregulated complement activation grows longer, it has become clear that targeted modulation of this innate immune system opens new windows of therapeutic opportunity for anti-inflammatory drug design. Indeed, the introduction of the first complement-targeting drugs has reignited a vibrant interest in the clinical translation of complement-based inhibitors. Compstatin was discovered as a cyclic peptide that inhibits complement activation by binding C3 and interfering with convertase formation and C3 cleavage. As the convergence point of all activation pathways and a molecular hub for crosstalk with multiple pathogenic pathways, C3 represents an attractive target for therapeutic modulation of the complement cascade. A multidisciplinary drug optimization effort encompassing rational wet' and in silico synthetic approaches and an array of biophysical, structural and analytical tools has culminated in an impressive structure-function refinement of compstatin, yielding a series of analogues that show promise for a wide spectrum of clinical applications. These new derivatives have improved inhibitory potency and pharmacokinetic profiles and show efficacy in clinically relevant primate models of disease. This review provides an up-to-date survey of the drug design effort placed on the compstatin family of C3 inhibitors, highlighting the most promising drug candidates. It also discusses translational challenges in complement drug discovery and peptide drug development and reviews concerns related to systemic C3 interception.

Keyword
clinical translation, complement-based drug design, compstatin, Cp40, nonhuman primate models, peptidic C3 inhibitors
National Category
Other Medical Sciences not elsewhere specified
Identifiers
urn:nbn:se:uu:diva-252456 (URN)10.1111/eci.12419 (DOI)000352008100007 ()25678219 (PubMedID)
Available from: 2015-05-07 Created: 2015-05-07 Last updated: 2017-12-04Bibliographically approved
Biglarnia, A., Yamamoto, S., Sedigh, A., Drachenberg, C., Wagner, M., Sund, F., . . . Larsson, E. (2015). Impact of duodenal cuff inflammation on outcome after clinical pancreas transplantation - a survey of a comprehensive follow-up strategy including serial protocol biopsy of the duodenal cuff. Paper presented at IPITA/IXA/CTS Joint Congress, NOV 15-19, 2015, Melbourne, AUSTRALIA. Xenotransplantation, 22, S15-S15
Open this publication in new window or tab >>Impact of duodenal cuff inflammation on outcome after clinical pancreas transplantation - a survey of a comprehensive follow-up strategy including serial protocol biopsy of the duodenal cuff
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2015 (English)In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, p. S15-S15Article in journal, Meeting abstract (Other academic) Published
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-276043 (URN)000364594100034 ()
Conference
IPITA/IXA/CTS Joint Congress, NOV 15-19, 2015, Melbourne, AUSTRALIA
Available from: 2016-02-09 Created: 2016-02-09 Last updated: 2017-11-30Bibliographically approved
Biglarnia, A., Yamamoto, S., Sedigh, A., Drachenberg, C., Wagner, M., Sund, F., . . . Larsson, E. (2015). Impact Of Duodenal Cuff Inflammation On Outcome After Clinical Pancreas Transplantation - A Survey Of A Comprehensive Follow-Up Strategy Including Serial Protocol Biopsy Of The Duodenal Cuff.. Paper presented at Joint Congress of the International-Pancreas-and-Islet-Transplantation-Association, International-Xenotransplantation-Association and Cell-Transplant-Society, NOV 15-19, 2015, Melbourne, AUSTRALIA. Transplantation, 99(11), S24-S24
Open this publication in new window or tab >>Impact Of Duodenal Cuff Inflammation On Outcome After Clinical Pancreas Transplantation - A Survey Of A Comprehensive Follow-Up Strategy Including Serial Protocol Biopsy Of The Duodenal Cuff.
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2015 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, no 11, p. S24-S24Article in journal, Meeting abstract (Other academic) Published
National Category
Immunology in the medical area Surgery
Identifiers
urn:nbn:se:uu:diva-281550 (URN)000368625700034 ()
Conference
Joint Congress of the International-Pancreas-and-Islet-Transplantation-Association, International-Xenotransplantation-Association and Cell-Transplant-Society, NOV 15-19, 2015, Melbourne, AUSTRALIA
Available from: 2016-04-05 Created: 2016-03-24 Last updated: 2018-01-10Bibliographically approved
Lorant, T., Bengtsson, M., Biglarnia, A., Eich, T., Eriksson, B.-M., Winstedt, L., . . . Tufveson, G. (2015). Rapid Removal Of Anti-Hla Antibodies In Immunized Patients Awaiting Renal Transplantation - A Dose Finding Study Of The Igg Degrading Enzyme Ides. Transplant International, 28, 73-73
Open this publication in new window or tab >>Rapid Removal Of Anti-Hla Antibodies In Immunized Patients Awaiting Renal Transplantation - A Dose Finding Study Of The Igg Degrading Enzyme Ides
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2015 (English)In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 28, p. 73-73Article in journal, Meeting abstract (Other academic) Published
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-281005 (URN)000367726700191 ()
Available from: 2016-03-16 Created: 2016-03-16 Last updated: 2017-11-30Bibliographically approved
Yamamoto, S., Sedigh, A. & Biglarnia, A.-R. (2015). Simultaneous Hand-Assisted Transperitoneal Bilateral Native Nephrectomy And Extracapsular Transplant Nephrectomy In A Patient With Polycystic Kidney Disease. Transplant International, 28, 216-216
Open this publication in new window or tab >>Simultaneous Hand-Assisted Transperitoneal Bilateral Native Nephrectomy And Extracapsular Transplant Nephrectomy In A Patient With Polycystic Kidney Disease
2015 (English)In: Transplant International, ISSN 0934-0874, E-ISSN 1432-2277, Vol. 28, p. 216-216Article in journal, Meeting abstract (Other academic) Published
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-281009 (URN)000367726701248 ()
Available from: 2016-03-16 Created: 2016-03-16 Last updated: 2017-11-30Bibliographically approved
Eriksson, O., Espes, D., Selvaraju, R. K., Jansson, E., Antoni, G., Sörensen, J., . . . Korsgren, O. (2014). The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas. Diabetes, 63(10), 3428-3437
Open this publication in new window or tab >>The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas
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2014 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 10, p. 3428-3437Article in journal (Refereed) Published
Abstract [en]

In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.

National Category
Other Basic Medicine
Identifiers
urn:nbn:se:uu:diva-224960 (URN)10.2337/db13-1877 (DOI)000342527300029 ()24848067 (PubMedID)
Available from: 2014-05-25 Created: 2014-05-25 Last updated: 2018-01-11Bibliographically approved
Biglarnia, A.-R., Bennet, W., Nilsson, T., Larsson, E., Magnusson, A., Yamamoto, S., . . . Tufveson, G. (2014). Utilization of Small Pediatric Donors Including Infants for Pancreas and Kidney Transplantation: Exemplification of the Surgical Technique and the Surveillance [Letter to the editor]. Annals of Surgery, 260(2), e5-7
Open this publication in new window or tab >>Utilization of Small Pediatric Donors Including Infants for Pancreas and Kidney Transplantation: Exemplification of the Surgical Technique and the Surveillance
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2014 (English)In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 260, no 2, p. e5-7Article in journal, Letter (Refereed) Published
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-225423 (URN)10.1097/SLA.0000000000000751 (DOI)000339173500005 ()24854454 (PubMedID)
Available from: 2014-06-03 Created: 2014-06-03 Last updated: 2017-12-05Bibliographically approved
Sjöberg, L., Biglarnia, A., Ahlström, H., Korsgren, O. & Weis, J. (2013). Assessing the Viability of Human Pancreas Grafts using 31P MR Spectroscopy - a Pilot Study. Paper presented at 14th World Congress of the International-Pancreas-and-Islet-Transplant-Association (IPITA), SEP 24-27, 2013, Monterey, CA. Transplantation, 96(6), S13-S13
Open this publication in new window or tab >>Assessing the Viability of Human Pancreas Grafts using 31P MR Spectroscopy - a Pilot Study
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2013 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 96, no 6, p. S13-S13Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-220757 (URN)000330443500025 ()
Conference
14th World Congress of the International-Pancreas-and-Islet-Transplant-Association (IPITA), SEP 24-27, 2013, Monterey, CA
Available from: 2014-03-20 Created: 2014-03-20 Last updated: 2017-12-05Bibliographically approved
Eriksson, O., Sjöberg, L., Ahlström, H., Antoni, G., Sörensen, J., Lubberink, M., . . . Korsgren, O. (2013). Functional Imaging of the Pancreatic Graft by Positron Emission Tomography. Paper presented at 14th World Congress of the International-Pancreas-and-Islet-Transplant-Association (IPITA), SEP 24-27, 2013, Monterey, CA. Transplantation, 96(6), S94-S94
Open this publication in new window or tab >>Functional Imaging of the Pancreatic Graft by Positron Emission Tomography
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2013 (English)In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 96, no 6, p. S94-S94Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-220746 (URN)000330443500171 ()
Conference
14th World Congress of the International-Pancreas-and-Islet-Transplant-Association (IPITA), SEP 24-27, 2013, Monterey, CA
Available from: 2014-03-24 Created: 2014-03-20 Last updated: 2017-12-05Bibliographically approved
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