Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Bone Mineral Density is Related to CD4+ T Cell Counts and Muscle Mass is Associated with B Cells in Common Variable Immunodeficiency Patients

Author(s): Daniel Barreto de Melo*, Rosa Maria Rodrigues Pereira, Bruno Sini, Débora Levy, Lilian Takayama, Cristina Maria Kokron, Ana Karolina Berselli Marinho, Octavio Grecco, Jorge Elias Kalil Filho and Myrthes Toledo Barros

Volume 24, Issue 2, 2024

Published on: 16 October, 2023

Page: [242 - 254] Pages: 13

DOI: 10.2174/1871530323666230822100031

Price: $65

Abstract

Background: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by chronic/recurrent respiratory infections, bronchiectasis, autoimmunity, inflammatory, gastrointestinal diseases and malignancies associated with a chronic inflammatory state and increased risk of osteoporosis and muscle loss.

Aim: The aim of this study was to evaluate bone mineral density (BMD), body composition and their relationship with lymphocyte subpopulations in CVID patients.

Methods: Dual-energy X-ray absorptiometry was performed to assess BMD, lean mass, and fat mass in CVID patients. Peripheral blood CD4+, CD8+, and CD19+ cells were measured using flow cytometry.

Results: Thirty-three patients (37.3 ± 10.8 years old) were examined. Although only 11.8% of the individuals were malnourished (BMI <18.5 kg/m2), 27.7% of them had low skeletal muscle mass index (SMI), and 57.6% of them had low BMD. Patients with osteopenia/osteoporosis presented lower weight (p = 0.007), lean mass (p = 0.011), appendicular lean mass (p = 0.011), SMI (p = 0.017), and CD4+ count (p = 0.030). Regression models showed a positive association between CD4+ count and bone/muscle parameters, whereas CD19+ B cell count was only associated with muscle variables. Analysis of ROC curves indicated a cutoff value of CD4+ count (657 cells/mm3; AUC: 0.71, 95% CI 0.52-0.90) which was related to low BMD. Weight (p = 0.004), lean mass (p = 0.027), appendicular lean mass (p = 0.022), SMI (p = 0.029), total bone mineral content (p = 0.005), lumbar (p = 0.005), femoral neck (p = 0.035), and total hip BMD (p<0.001) were found to be lower in patients with CD4+ count below the cutoff.

Conclusion: CVID patients presented with low BMD, which was associated with CD4+ count. Moreover, low muscle parameters were correlated with B cell count.

Keywords: Bone mineral density, osteoporosis, lean mass, CD4+ T cells, B cells, common variable immunodeficiency.

Graphical Abstract
[1]
Bonilla, F.A.; Barlan, I.; Chapel, H.; Costa-Carvalho, B.T.; Cunningham-Rundles, C.; de la Morena, M.T.; Espinosa-Rosales, F.J.; Hammarström, L.; Nonoyama, S.; Quinti, I.; Routes, J.M.; Tang, M.L.K.; Warnatz, K. International consensus document (ICON): Common variable immunodeficiency disorders. J. Allergy Clin. Immunol. Pract., 2016, 4(1), 38-59.
[http://dx.doi.org/10.1016/j.jaip.2015.07.025] [PMID: 26563668]
[2]
Ameratunga, R.; Allan, C.; Woon, S.T. Defining common variable immunodeficiency disorders in 2020. Immunol. Allergy Clin. North Am., 2020, 40(3), 403-420.
[http://dx.doi.org/10.1016/j.iac.2020.03.001] [PMID: 32654689]
[3]
Lee, T.K.; Gereige, J.D.; Maglione, P.J. State-of-the-art diagnostic evaluation of common variable immunodeficiency. Ann. Allergy Asthma Immunol., 2021, 127(1), 19-27.
[http://dx.doi.org/10.1016/j.anai.2021.03.005] [PMID: 33716149]
[4]
Cunningham-Rundles, C.; Bodian, C. Common variable immunodeficiency: Clinical and immunological features of 248 patients. Clin. Immunol., 1999, 92(1), 34-48.
[http://dx.doi.org/10.1006/clim.1999.4725] [PMID: 10413651]
[5]
Yesillik, S.; Agrawal, S.; Gollapudi, S.V.; Gupta, S. Phenotypic analysis of CD4+ Treg, CD8+ Treg, and breg cells in adult common variable immunodeficiency patients. Int. Arch. Allergy Immunol., 2019, 180(2), 150-158.
[http://dx.doi.org/10.1159/000501457] [PMID: 31284281]
[6]
Resnick, E.S.; Moshier, E.L.; Godbold, J.H.; Cunningham-Rundles, C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood, 2012, 119(7), 1650-1657.
[http://dx.doi.org/10.1182/blood-2011-09-377945] [PMID: 22180439]
[7]
Szczawińska-Popłonyk, A.; Ta̧polska-Jóźwiak, K.; Schwartzmann, E.; Popłonyk, N. Immune dysregulation in pediatric common variable immunodeficiency: Implications for the diagnostic approach. Front Pediatr., 2022, 10, 855200.
[http://dx.doi.org/10.3389/fped.2022.855200] [PMID: 35402361]
[8]
Baris, S.; Ozen, A.; Ercan, H.; Karakoc-Aydiner, E.; Cagan, H.; Ozdemir, C.; Barlan, M.; Bahceciler, N.N.; Barlan, I.B. Osteoporosis: An ignored complication of CVID. Pediatr. Allergy Immunol., 2011, 22(7), 676-683.
[http://dx.doi.org/10.1111/j.1399-3038.2011.01187.x] [PMID: 21645119]
[9]
Ayteki̇n, G.; Çölkesen, F.; Yildiz, E.; Arslan, Ş.; Çalişkaner, A.Z. Bone metabolism alterations in patients with common variable immune deficiency: A retrospective cohort study. Asthma Allergy Immunology, 2020, 18(2), 66-72.
[http://dx.doi.org/10.21911/aai.501]
[10]
Mohebbi, A.; Azizi, G.; Tavakolinia, N.; Abbasi, F.; Sayarifard, F.; Karimipour, M.; Kiaee, F.; Yazdani, R.; Ebrahimi, S.S.; Ebrahimi, M.; Rafiemanesh, H.; Tafaroji, J.; Ziaee, V.; Abolhassani, H.; Aghamohammadi, A. Comparison of bone mineral density in common variable immunodeficiency and x-linked agammaglobulinaemia patients. Endocr. Metab. Immune Disord. Drug Targets, 2017, 17(2), 134-140.
[PMID: 28606051]
[11]
Briot, K.; Geusens, P. Em Bultink, I.; Lems, W.F.; Roux, C. Inflammatory diseases and bone fragility. Osteoporos. Int., 2017, 28(12), 3301-3314.
[http://dx.doi.org/10.1007/s00198-017-4189-7] [PMID: 28916915]
[12]
Li, Y.; Toraldo, G.; Li, A.; Yang, X.; Zhang, H.; Qian, W.P.; Weitzmann, M.N. B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo. Blood, 2007, 109(9), 3839-3848.
[http://dx.doi.org/10.1182/blood-2006-07-037994] [PMID: 17202317]
[13]
Sowerwine, K.J.; Shaw, P.A.; Gu, W.; Ling, J.C.; Collins, M.T.; Darnell, D.N.; Anderson, V.L.; Davis, J.; Hsu, A.; Welch, P.; Puck, J.M.; Holland, S.M.; Freeman, A.F. Bone density and fractures in autosomal dominant hyper IgE syndrome. J. Clin. Immunol., 2014, 34(2), 260-264.
[http://dx.doi.org/10.1007/s10875-013-9982-2] [PMID: 24402620]
[14]
Lopez-Granados, E.; Temmerman, S.T.; Wu, L.; Reynolds, J.C.; Follmann, D.; Liu, S.; Nelson, D.L.; Rauch, F.; Jain, A. Osteopenia in X-linked hyper-IgM syndrome reveals a regulatory role for CD40 ligand in osteoclastogenesis. Proc. Natl. Acad. Sci., 2007, 104(12), 5056-5061.
[http://dx.doi.org/10.1073/pnas.0605715104] [PMID: 17360404]
[15]
Cascio, A.; Colomba, C.; Di Carlo, P.; Serra, N.; Lo Re, G.; Gambino, A.; Lo Casto, A.; Guglielmi, G.; Veronese, N.; Lagalla, R.; Sergi, C. Low bone mineral density in HIV-positive young Italians and migrants. PLoS One, 2020, 15(9), e0237984.
[http://dx.doi.org/10.1371/journal.pone.0237984] [PMID: 32881882]
[16]
Pramukti, I.; Lindayani, L.; Chen, Y.C.; Yeh, C.Y.; Tai, T.W.; Fetzer, S.; Ko, N.Y. Bone fracture among people living with HIV: A systematic review and meta-regression of prevalence, incidence, and risk factors. PLoS One, 2020, 15(6), e0233501.
[http://dx.doi.org/10.1371/journal.pone.0233501] [PMID: 32497105]
[17]
Goh, S.S.L.; Lai, P.S.M.; Tan, A.T.B.; Ponnampalavanar, S. Reduced bone mineral density in human immunodeficiency virus-infected individuals: a meta-analysis of its prevalence and risk factors: Supplementary presentation. Osteoporos. Int., 2018, 29(7), 1683.
[http://dx.doi.org/10.1007/s00198-018-4379-y] [PMID: 29737369]
[18]
Berbers, R.M.; van der Wal, M.M.; van Montfrans, J.M.; Ellerbroek, P.M.; Dalm, V.A.S.H.; van Hagen, P.M.; Leavis, H.L.; van Wijk, F. Chronically activated T-cells retain their inflammatory properties in common variable immunodeficiency. J. Clin. Immunol., 2021, 41(7), 1621-1632.
[http://dx.doi.org/10.1007/s10875-021-01084-6] [PMID: 34247288]
[19]
Litzman, J.; Nechvatalova, J.; Xu, J.; Ticha, O.; Vlkova, M.; Hel, Z. Chronic immune activation in common variable immunodeficiency (CVID) is associated with elevated serum levels of soluble CD14 and CD25 but not endotoxaemia. Clin. Exp. Immunol., 2012, 170(3), 321-332.
[http://dx.doi.org/10.1111/j.1365-2249.2012.04655.x] [PMID: 23121673]
[20]
World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Heal. Organ. -. Tech. Rep. Ser., 2000, 894, i-xii, 1-253.
[21]
Eastell, R.; Schini, M. Prevention and management of osteoporosis. Med., 2021, 49, 572-577.
[22]
Leib, E.S.; Lewiecki, E.M.; Binkley, N.; Hamdy, R.C. Official positions of the international society for clinical densitometry. South. Med. J., 2004, 97(1), 107-110.
[http://dx.doi.org/10.1097/00007611-200401000-00029] [PMID: 14746436]
[23]
Baumgartner, R.N.; Koehler, K.M.; Gallagher, D.; Romero, L.; Heymsfield, S.B.; Ross, R.R.; Garry, P.J.; Lindeman, R.D. Epidemiology of sarcopenia among the elderly in New Mexico. Am. J. Epidemiol., 1998, 147(8), 755-763.
[http://dx.doi.org/10.1093/oxfordjournals.aje.a009520] [PMID: 9554417]
[24]
Andy, B.M.K. A language and environment for statistical computing. 2017, 10, 11-18.
[25]
Muscaritoli, M.; Fanfarillo, F.; Luzi, G.; Sirianni, M.C.; Iebba, F.; Laviano, A.; Russo, M.; Aiuti, F.; Fanelli, F.R. Impaired nutritional status in common variable immunodeficiency patients correlates with reduced levels of serum IgA and of circulating CD4+ T lymphocytes. Eur. J. Clin. Invest., 2001, 31(6), 544-549.
[http://dx.doi.org/10.1046/j.1365-2362.2001.00838.x] [PMID: 11422405]
[26]
Vieira, D.G.; Costa-Carvalho, B.T.; Hix, S.; da Silva, R.; Correia, M.S.G.; Sarni, R.O.S. Higher cardiovascular risk in common variable immunodeficiency and x-linked agammaglobulinaemia patients. Ann. Nutr. Metab., 2015, 66(4), 237-241.
[http://dx.doi.org/10.1159/000435818] [PMID: 26183722]
[27]
Kouhkan, A.; Pourpak, Z.; Moin, M.; Dorosty, A.R.; Safaralizadeh, R.; Teimorian, S.; Farhoudi, A.; Aghamohammadi, A.; Mesdaghi, M.; Kazemnejad, A. A study of malnutrition in Iranian patients with primary antibody deficiency. Iran. J. Allergy Asthma Immunol., 2004, 3(4), 189-196.
[PMID: 17301413]
[28]
Yıldız, E.; Arslan, Ş.; Çölkesen, F.; Sadi Aykan, F.; Evcen, R.; Kılınç, M.; Aytekin, G. Evaluation of malnutrition risk and nutrition status in adult patients with common variable immunodeficiency. Nutr. Clin. Pract., 2022, 37(5), 1206-1214.
[http://dx.doi.org/10.1002/ncp.10806] [PMID: 34989028]
[29]
Donini, L.M.; Busetto, L.; Bischoff, S.C.; Cederholm, T.; Ballesteros-Pomar, M.D.; Batsis, J.A.; Bauer, J.M.; Boirie, Y.; Cruz-Jentoft, A.J.; Dicker, D.; Frara, S.; Frühbeck, G.; Genton, L.; Gepner, Y.; Giustina, A.; Gonzalez, M.C.; Han, H.S.; Heymsfield, S.B.; Higashiguchi, T.; Laviano, A.; Lenzi, A.; Nyulasi, I.; Parrinello, E.; Poggiogalle, E.; Prado, C.M.; Salvador, J.; Rolland, Y.; Santini, F.; Serlie, M.J.; Shi, H.; Sieber, C.C.; Siervo, M.; Vettor, R.; Villareal, D.T.; Volkert, D.; Yu, J.; Zamboni, M.; Barazzoni, R. Definition and diagnostic criteria for sarcopenic obesity: ESPEN and EASO consensus statement. Clin. Nutr., 2022, 41(4), 990-1000.
[http://dx.doi.org/10.1016/j.clnu.2021.11.014] [PMID: 35227529]
[30]
Gao, Q.; Mei, F.; Shang, Y.; Hu, K.; Chen, F.; Zhao, L.; Ma, B. Global prevalence of sarcopenic obesity in older adults: A systematic review and meta-analysis. Clin. Nutr., 2021, 40(7), 4633-4641.
[http://dx.doi.org/10.1016/j.clnu.2021.06.009] [PMID: 34229269]
[31]
Abete, I.; Konieczna, J.; Zulet, M.A.; Galmés-Panades, A.M.; Ibero-Baraibar, I.; Babio, N.; Estruch, R.; Vidal, J.; Toledo, E.; Razquin, C.; Bartolomé, R.; Díaz-Lopez, A.; Fiol, M.; Casas, R.; Vera, J.; Buil-Cosiales, P.; Pintó, X.; Corbella, E.; Portillo, M.P.; Paz, J.A.; Martín, V.; Daimiel, L.; Goday, A.; Rosique-Esteban, N.; Salas-Salvadó, J.; Romaguera, D.; Martínez, J.A. Association of lifestyle factors and inflammation with sarcopenic obesity: data from the PREDIMED‐Plus trial. J. Cachexia Sarcopenia Muscle, 2019, 10(5), 974-984.
[http://dx.doi.org/10.1002/jcsm.12442] [PMID: 31144432]
[32]
Karanth, S.D.; Washington, C.; Cheng, T.Y.D.; Zhou, D.; Leeuwenburgh, C.; Braithwaite, D.; Zhang, D. Inflammation in relation to sarcopenia and sarcopenic obesity among older adults living with chronic comorbidities: Results from the national health and nutrition examination survey 1999-2006. Nutrients, 2021, 13(11), 3957.
[http://dx.doi.org/10.3390/nu13113957] [PMID: 34836213]
[33]
Hel, Z.; Huijbregts, R.P.H.; Xu, J.; Nechvatalova, J.; Vlkova, M.; Litzman, J. Altered serum cytokine signature in common variable immunodeficiency. J. Clin. Immunol., 2014, 34(8), 971-978.
[http://dx.doi.org/10.1007/s10875-014-0099-z] [PMID: 25246148]
[34]
Berbers, R.M.; Drylewicz, J.; Ellerbroek, P.M.; van Montfrans, J.M.; Dalm, V.A.S.H.; van Hagen, P.M.; Keller, B.; Warnatz, K.; van de Ven, A.; van Laar, J.M.; Nierkens, S.; Leavis, H.L. Targeted proteomics reveals inflammatory pathways that classify immune dysregulation in common variable immunodeficiency. J. Clin. Immunol., 2021, 41(2), 362-373.
[http://dx.doi.org/10.1007/s10875-020-00908-1] [PMID: 33190167]
[35]
Oliveira, V.H.F.; Borsari, A.L.; Webel, A.R.; Erlandson, K.M.; Deminice, R. Sarcopenia in people living with the Human Immunodeficiency Virus: A systematic review and meta-analysis. Eur. J. Clin. Nutr., 2020, 74(7), 1009-1021.
[http://dx.doi.org/10.1038/s41430-020-0637-0] [PMID: 32341489]
[36]
de Almeida, L.L.; Ilha, T.A.S.H.; de Carvalho, J.A.M.; Stein, C.; Caeran, G.; Comim, F.V.; Moresco, R.N.; Haygert, C.J.P.; Compston, J.E.; Premaor, M.O. Sarcopenia and its association with vertebral fractures in people living with HIV. Calcif. Tissue Int., 2020, 107(3), 249-256.
[http://dx.doi.org/10.1007/s00223-020-00718-y] [PMID: 32683475]
[37]
Hegelund, M.H.; Faurholt-Jepsen, D.; Abdissa, A.; Yilma, D.; Andersen, Å.B.; Christensen, D.L.; Wells, J.C.; Friis, H.; Girma, T.; Olsen, M.F. Inflammatory markers as correlates of body composition and grip strength among adults with and without HIV: A cross-sectional study in Ethiopia. Eur. J. Clin. Nutr., 2022, 76(7), 973-978.
[http://dx.doi.org/10.1038/s41430-021-01056-4] [PMID: 35022553]
[38]
Jørgensen, S.F.; Trøseid, M.; Kummen, M.; Anmarkrud, J.A.; Michelsen, A.E.; Osnes, L.T.; Holm, K.; Høivik, M.L.; Rashidi, A.; Dahl, C.P.; Vesterhus, M.; Halvorsen, B.; Mollnes, T.E.; Berge, R.K.; Moum, B.; Lundin, K.E.A.; Fevang, B.; Ueland, T.; Karlsen, T.H.; Aukrust, P.; Hov, J.R. Altered gut microbiota profile in common variable immunodeficiency associates with levels of lipopolysaccharide and markers of systemic immune activation. Mucosal Immunol., 2016, 9(6), 1455-1465.
[http://dx.doi.org/10.1038/mi.2016.18] [PMID: 26982597]
[39]
Holm, A.M.; Aukrust, P.; Damås, J.K.; Müller, F.; Halvorsen, B.; Frøland, S.S. Abnormal interleukin-7 function in common variable immunodeficiency. Blood, 2005, 105(7), 2887-2890.
[http://dx.doi.org/10.1182/blood-2004-06-2423] [PMID: 15598813]
[40]
Barbosa, R.R.; Silva, S.P.; Silva, S.L.; Tendeiro, R.; Melo, A.C.; Pedro, E.; Barbosa, M.P.; Santos, M.C.P.; Victorino, R.M.M.; Sousa, A.E. Monocyte activation is a feature of common variable immunodeficiency irrespective of plasma lipopolysaccharide levels. Clin. Exp. Immunol., 2012, 169(3), 263-272.
[http://dx.doi.org/10.1111/j.1365-2249.2012.04620.x] [PMID: 22861366]
[41]
AlQranei, M.S.; Senbanjo, L.T.; Aljohani, H.; Hamza, T.; Chellaiah, M.A. Lipopolysaccharide- TLR-4 axis regulates osteoclastogenesis independent of RANKL/RANK signaling. BMC Immunol., 2021, 22(1), 23.
[http://dx.doi.org/10.1186/s12865-021-00409-9] [PMID: 33765924]
[42]
van Roon, J.A.G.; Lafeber, F.P.J.G. Role of interleukin-7 in degenerative and inflammatory joint diseases. Arthritis Res. Ther., 2008, 10(2), 107.
[http://dx.doi.org/10.1186/ar2395] [PMID: 18466642]
[43]
Yokota, K.; Sato, K.; Miyazaki, T.; Aizaki, Y.; Tanaka, S.; Sekikawa, M.; Kozu, N.; Kadono, Y.; Oda, H.; Mimura, T. Characterization and function of tumor necrosis factor and interleukin‐6-induced osteoclasts in rheumatoid arthritis. Arthritis Rheumatol., 2021, 73(7), 1145-1154.
[http://dx.doi.org/10.1002/art.41666] [PMID: 33512089]
[44]
Tang, Y.; Peng, B.; Liu, J.; Liu, Z.; Xia, Y.; Geng, B. Systemic immune-inflammation index and bone mineral density in postmenopausal women: A cross-sectional study of the national health and nutrition examination survey (NHANES) 2007-2018. Front. Immunol., 2022, 13, 975400.
[http://dx.doi.org/10.3389/fimmu.2022.975400] [PMID: 36159805]
[45]
Anderson, D.M.; Maraskovsky, E.; Billingsley, W.L.; Dougall, W.C.; Tometsko, M.E.; Roux, E.R.; Teepe, M.C.; DuBose, R.F.; Cosman, D.; Galibert, L. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature, 1997, 390(6656), 175-179.
[http://dx.doi.org/10.1038/36593] [PMID: 9367155]
[46]
Hsu, H.; Lacey, D.L.; Dunstan, C.R.; Solovyev, I.; Colombero, A.; Timms, E.; Tan, H.L.; Elliott, G.; Kelley, M.J.; Sarosi, I.; Wang, L.; Xia, X.Z.; Elliott, R.; Chiu, L.; Black, T.; Scully, S.; Capparelli, C.; Morony, S.; Shimamoto, G.; Bass, M.B.; Boyle, W.J. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc. Natl. Acad. Sci., 1999, 96(7), 3540-3545.
[http://dx.doi.org/10.1073/pnas.96.7.3540] [PMID: 10097072]
[47]
Onal, M.; Xiong, J.; Chen, X.; Thostenson, J.D.; Almeida, M.; Manolagas, S.C.; O’Brien, C.A. Receptor activator of nuclear factor κB ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomy-induced bone loss. J. Biol. Chem., 2012, 287(35), 29851-29860.
[http://dx.doi.org/10.1074/jbc.M112.377945] [PMID: 22782898]
[48]
Simonet, W.S.; Lacey, D.L.; Dunstan, C.R.; Kelley, M.; Chang, M.S.; Lüthy, R.; Nguyen, H.Q.; Wooden, S.; Bennett, L.; Boone, T.; Shimamoto, G.; DeRose, M.; Elliott, R.; Colombero, A.; Tan, H.L.; Trail, G.; Sullivan, J.; Davy, E.; Bucay, N.; Renshaw-Gegg, L.; Hughes, T.M.; Hill, D.; Pattison, W.; Campbell, P.; Sander, S.; Van, G.; Tarpley, J.; Derby, P.; Lee, R.; Boyle, W.J. Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell, 1997, 89(2), 309-319.
[http://dx.doi.org/10.1016/S0092-8674(00)80209-3] [PMID: 9108485]
[49]
Nishida, D.; Arai, A.; Zhao, L.; Yang, M.; Nakamichi, Y.; Horibe, K.; Hosoya, A.; Kobayashi, Y.; Udagawa, N.; Mizoguchi, T. RANKL/OPG ratio regulates odontoclastogenesis in damaged dental pulp. Sci. Rep., 2021, 11(1), 4575.
[http://dx.doi.org/10.1038/s41598-021-84354-y] [PMID: 33633362]
[50]
Cohen, S.B.; Dore, R.K.; Lane, N.E.; Ory, P.A.; Peterfy, C.G.; Sharp, J.T.; van der Heijde, D.; Zhou, L.; Tsuji, W.; Newmark, R. Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: A twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum., 2008, 58(5), 1299-1309.
[http://dx.doi.org/10.1002/art.23417] [PMID: 18438830]
[51]
Deodhar, A.; Dore, R.K.; Mandel, D.; Schechtman, J.; Shergy, W.; Trapp, R.; Ory, P.A.; Peterfy, C.G.; Fuerst, T.; Wang, H.; Zhou, L.; Tsuji, W.; Newmark, R. Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients. Arthritis Care Res., 2010, 62(4), 569-574.
[http://dx.doi.org/10.1002/acr.20004] [PMID: 20391513]
[52]
Makras, P.; Petrikkos, P.; Anastasilakis, A.D.; Kolynou, A.; Katsarou, A.; Tsachouridou, O.; Metallidis, S.; Yavropoulou, M.P. Denosumab versus zoledronate for the treatment of low bone mineral density in male HIV-infected patients. Bone Rep., 2021, 15, 101128.
[http://dx.doi.org/10.1016/j.bonr.2021.101128] [PMID: 34541262]
[53]
Mok, C.C.; Ho, L.Y.; Leung, S.M.T.; Cheung, H.N.; Chen, S.P.L.; Ma, K.M. Denosumab versus alendronate in long-term glucocorticoid users: A 12-month randomized controlled trial. Bone, 2021, 146, 115902.
[http://dx.doi.org/10.1016/j.bone.2021.115902] [PMID: 33631355]
[54]
Eller-Vainicher, C.; Palmieri, S.; Cairoli, E.; Goggi, G.; Scillitani, A.; Arosio, M.; Falchetti, A.; Chiodini, I. Protective effect of denosumab on bone in older women with primary hyperparathyroidism. J. Am. Geriatr. Soc., 2018, 66(3), 518-524.
[http://dx.doi.org/10.1111/jgs.15250] [PMID: 29364518]
[55]
Laroche, M.; Baradat, C.; Ruyssen-Witrand, A.; Degboe, Y. Variability of Denosumab densitometric response in postmenopausal osteoporosis. Rheumatol. Int., 2018, 38(3), 461-466.
[http://dx.doi.org/10.1007/s00296-018-3929-0] [PMID: 29362876]
[56]
Gnant, M.; Pfeiler, G.; Steger, G.G.; Egle, D.; Greil, R.; Fitzal, F.; Wette, V.; Balic, M.; Haslbauer, F.; Melbinger-Zeinitzer, E.; Bjelic-Radisic, V.; Jakesz, R.; Marth, C.; Sevelda, P.; Mlineritsch, B.; Exner, R.; Fesl, C.; Frantal, S.; Singer, C.F. Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): Disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol., 2019, 20(3), 339-351.
[http://dx.doi.org/10.1016/S1470-2045(18)30862-3] [PMID: 30795951]
[57]
Farlay, D.; Rizzo, S.; Dempster, D.W.; Huang, S.; Chines, A.; Brown, J.P.; Boivin, G. Bone mineral and organic properties in postmenopausal women treated with denosumab for up to 10 years. J. Bone Miner. Res., 2022, 37(5), 856-864.
[http://dx.doi.org/10.1002/jbmr.4538] [PMID: 35249242]
[58]
Ueland, T.; Frøland, S.S.; Bollerslev, J.; Aukrust, P. Increased levels of biochemical markers of bone turnover in relation to persistent immune activation in common variable immunodeficiency. Eur. J. Clin. Invest., 2001, 31(1), 72-78.
[http://dx.doi.org/10.1046/j.1365-2362.2001.00768.x] [PMID: 11168441]
[59]
Titanji, K.; Vunnava, A.; Sheth, A.N.; Delille, C.; Lennox, J.L.; Sanford, S.E.; Foster, A.; Knezevic, A.; Easley, K.A.; Weitzmann, M.N.; Ofotokun, I.; Dysregulated, B. Dysregulated B cell expression of RANKL and OPG correlates with loss of bone mineral density in HIV infection. PLoS Pathog., 2014, 10(11), e1004497.
[http://dx.doi.org/10.1371/journal.ppat.1004497] [PMID: 25393853]
[60]
Li, G.; Lin, J.; Zhang, C.; Gao, H.; Lu, H.; Gao, X.; Zhu, R.; Li, Z.; Li, M.; Liu, Z. Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease. Gut Microbes, 2021, 13(1), 1968257.
[http://dx.doi.org/10.1080/19490976.2021.1968257] [PMID: 34494943]
[61]
Furusawa, Y.; Obata, Y.; Fukuda, S.; Endo, T.A.; Nakato, G.; Takahashi, D.; Nakanishi, Y.; Uetake, C.; Kato, K.; Kato, T.; Takahashi, M.; Fukuda, N.N.; Murakami, S.; Miyauchi, E.; Hino, S.; Atarashi, K.; Onawa, S.; Fujimura, Y.; Lockett, T.; Clarke, J.M.; Topping, D.L.; Tomita, M.; Hori, S.; Ohara, O.; Morita, T.; Koseki, H.; Kikuchi, J.; Honda, K.; Hase, K.; Ohno, H. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature, 2013, 504(7480), 446-450.
[http://dx.doi.org/10.1038/nature12721] [PMID: 24226770]
[62]
Tyagi, A.M.; Yu, M.; Darby, T.M.; Vaccaro, C.; Li, J.Y.; Owens, J.A.; Hsu, E.; Adams, J.; Weitzmann, M.N.; Jones, R.M.; Pacifici, R. The microbial metabolite butyrate stimulates bone formation via T regulatory cell-mediated regulation of WNT10B expression. Immunity, 2018, 49(6), 1116-1131.e7.
[http://dx.doi.org/10.1016/j.immuni.2018.10.013] [PMID: 30446387]
[63]
Fiedorová, K.; Radvanský, M.; Bosák, J. Grombiříková, H.; Němcová, E.; Králíčková, P.; Černochová, M.; Kotásková, I.; Lexa, M.; Litzman, J.; Šmajs, D.; Freiberger, T. Bacterial but not fungal gut microbiota alterations are associated with common variable immunodeficiency (CVID) phenotype. Front. Immunol., 2019, 10, 1914.
[http://dx.doi.org/10.3389/fimmu.2019.01914] [PMID: 31456808]
[64]
Macpherson, M.E.; Hov, J.R.; Ueland, T.; Dahl, T.B.; Kummen, M.; Otterdal, K.; Holm, K.; Berge, R.K.; Mollnes, T.E.; Trøseid, M.; Halvorsen, B.; Aukrust, P.; Fevang, B.; Jørgensen, S.F. Gut microbiota-dependent trimethylamine N-oxide associates with inflammation in common variable immunodeficiency. Front. Immunol., 2020, 11, 574500.
[http://dx.doi.org/10.3389/fimmu.2020.574500] [PMID: 33042155]
[65]
Panach, L.; Pineda, B.; Mifsut, D.; Tarín, J.J.; Cano, A.; García-Pérez, M.Á. The role of CD40 and CD40L in bone mineral density and in osteoporosis risk: A genetic and functional study. Bone, 2016, 83, 94-103.
[http://dx.doi.org/10.1016/j.bone.2015.11.002] [PMID: 26545336]
[66]
Forrester, J.E.; Spiegelman, D.; Woods, M.; Knox, T.A.; Fauntleroy, J.M.; Gorbach, S.L. Weight and body composition in a cohort of HIV-positive men and women. Public Health Nutr., 2001, 4(3), 743-747.
[http://dx.doi.org/10.1079/PHN200099] [PMID: 11415480]
[67]
Wrottesley, S.V.; Micklesfield, L.K.; Hamill, M.M.; Goldberg, G.R.; Prentice, A.; Pettifor, J.M.; Norris, S.A.; Feeley, A.B. Dietary intake and body composition in HIV-positive and -negative South African women. Public Health Nutr., 2014, 17(7), 1603-1613.
[http://dx.doi.org/10.1017/S1368980013001808] [PMID: 23835214]
[68]
Grant, P.M.; Kitch, D.; McComsey, G.A.; Collier, A.C.; Bartali, B.; Koletar, S.L.; Erlandson, K.M.; Lake, J.E.; Yin, M.T.; Melbourne, K.; Ha, B.; Brown, T.T. Long-term body composition changes in antiretroviral-treated HIV-infected individuals. AIDS, 2016, 30(18), 2805-2813.
[http://dx.doi.org/10.1097/QAD.0000000000001248] [PMID: 27662545]
[69]
Almeida, T.S.; Cortez, A.F.; Cruz, M.R.; Almeida, V.P. Predictors of sarcopenia in young hospitalized patients living with HIV. Braz. J. Infect. Dis., 2021, 25(2), 101574.
[http://dx.doi.org/10.1016/j.bjid.2021.101574] [PMID: 33861970]
[70]
Akgün, K.M.; Krishnan, S.; Butt, A.A.; Gibert, C.L.; Graber, C.J.; Huang, L.; Pisani, M.A.; Rodriguez-Barradas, M.C.; Hoo, G.W.S.; Justice, A.C.; Crothers, K.; Tate, J.P. CD4+ cell count and outcomes among HIV-infected compared with uninfected medical ICU survivors in a national cohort. AIDS, 2021, 35(14), 2355-2365.
[http://dx.doi.org/10.1097/QAD.0000000000003019] [PMID: 34261095]
[71]
Cudrici, C.D.; Boulougoura, A.; Sheikh, V.; Freeman, A.; Sortino, O.; Katz, J.D.; Sereti, I.; Siegel, R.M. Characterization of autoantibodies, immunophenotype and autoimmune disease in a prospective cohort of patients with idiopathic CD4 lymphocytopenia. Clin. Immunol., 2021, 224, 108664.
[http://dx.doi.org/10.1016/j.clim.2021.108664] [PMID: 33422677]
[72]
Yarmohammadi, H.; Cunningham-Rundles, C. Idiopathic CD4 lymphocytopenia. Ann. Allergy Asthma Immunol., 2017, 119(4), 374-378.
[http://dx.doi.org/10.1016/j.anai.2017.07.021] [PMID: 28958376]
[73]
Giovannetti, A.; Pierdominici, M.; Mazzetta, F.; Marziali, M.; Renzi, C.; Mileo, A.M.; De Felice, M.; Mora, B.; Esposito, A.; Carello, R.; Pizzuti, A.; Paggi, M.G.; Paganelli, R.; Malorni, W.; Aiuti, F. Unravelling the complexity of T cell abnormalities in common variable immunodeficiency. J. Immunol., 2007, 178(6), 3932-3943.
[http://dx.doi.org/10.4049/jimmunol.178.6.3932] [PMID: 17339494]
[74]
Shavit, R.; Maoz-Segal, R.; Prizinsky, S.; Haj-Yahia, S.; Offengenden, I.; Machnas-Mayan, D.; Tunisky, Y.; Iancovici-Kidon, M.; Agmon-Levin, N. Immunodeficiency (CVID and CD4 lymphopenia) is associated with a high risk of malignancy among adults with primary immune deficiency. Clin. Exp. Immunol., 2021, 204(2), 251-257.
[http://dx.doi.org/10.1111/cei.13579] [PMID: 33497464]
[75]
Malphettes, M.; Gérard, L.; Carmagnat, M.; Mouillot, G.; Vince, N.; Boutboul, D.; Bérezné, A.; Nove-Josserand, R.; Lemoing, V.; Tetu, L.; Viallard, J.F.; Bonnotte, B.; Pavic, M.; Haroche, J.; Larroche, C.; Brouet, J.C.; Fermand, J.P.; Rabian, C.; Fieschi, C.; Oksenhendler, E. Late-onset combined immune deficiency: A subset of common variable immunodeficiency with severe T cell defect. Clin. Infect. Dis., 2009, 49(9), 1329-1338.
[http://dx.doi.org/10.1086/606059] [PMID: 19807277]
[76]
Morgan, D.; Tergaonkar, V. Unraveling B cell trajectories at single cell resolution. Trends Immunol., 2022, 43(3), 210-229.
[http://dx.doi.org/10.1016/j.it.2022.01.003] [PMID: 35090788]
[77]
Matson, E.M.; Abyazi, M.L.; Bell, K.A.; Hayes, K.M.; Maglione, P.J. B cell dysregulation in common variable immunodeficiency interstitial lung disease. Front. Immunol., 2021, 11, 622114.
[http://dx.doi.org/10.3389/fimmu.2020.622114] [PMID: 33613556]
[78]
Tuttle, C.S.L.; Thang, L.A.N.; Maier, A.B. Markers of inflammation and their association with muscle strength and mass: A systematic review and meta-analysis. Ageing Res. Rev., 2020, 64, 101185.
[http://dx.doi.org/10.1016/j.arr.2020.101185] [PMID: 32992047]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy