Human Immune Disorders Group


The immune system can be viewed as an internal machine with the different parts working together to fight off threats from invading pathogens. We know that this complex array of interactions is usually very effective, as although we are likely to be faced with antigenic insults on a daily basis, we are rarely fraught by infection.

However, on occasion, and some people more frequently than others, we do succumb to infection. This can be compounded by factors such as stress, lack of sleep or poor diet, but the underlying cause is that our immune system has failed at doing its job. Whenever we are faced with a pathogen our immune system has to recognise this pathogen as a foreign body, what type it is and decide what is the best way of dealing with it. It is imperative that we dissect and understand the different mechanisms of the immune response such that we can identify appropriate therapies for disease treatment and prevention such as with vaccines.

We have chosen to study the workings of the immune system by investigating primary human imunodeficiencies. These are patients with mutations in a single gene, which renders them vulnerable to infection. Depending on the gene, the affected patient can present with quite severe disease. An example of this would be the “boy in the bubble” who had severe combined immunodeficiency (SCID) due to a mutation in IL-2RG or the common gamma chain. However, surprisingly, in some instances patients with these gene mutations do not present with overwhelming immunodeficiency, but rather they display susceptibility to a very narrow spectrum of infections.

For example patients with mutations in the gene encoding a protein termed SAP are only susceptible to infection with Epstein Barr virus (EBV), which causes glandular fever. In fact, by studying patients with defects in SAP expression, we have gained invaluable insight into how the immune system deals with EBV infections. Through investigating patients with immunodeficiencies we hope to establish the type of responses required for the elimination of different pathogens and identify novel therapies for the treatment of immunodeficiencies and other diseases whereby the immune system is compromised.

Selected Publications

Ma C. Human T Follicular Helper Cells in Primary Immunodeficiency:Quality Just as Important as Quantity. J Clin Immunol (Published online 3rd March 2016).

S Okada, Markle JG, Deenick EK, Mele F, Averbuch D, Lagos M, Alzahrani M, Al-Muhsen S, Halwani R, Ma CS, Wong N, Soudais C, Henderson L, Marzouqa H, Shamma J, Gonzalez M, Martinez-Baricarte R, Okada C, Avery DT, Latorre D, Deswarte C, Jabot-Hanin F, Torrado E, Fountain J, Belkadi A, Itan Y, Boisson B, Migaud M, Lindestam Arlehamn CS, Sette A, Breton S, McCluskey J, Rossjohn J, de Villartay J-P, Moshous D, Hambleton S, Latour S, Arkwright P, Picard C, Lantz O, Engelhard D, Kobayashi M, Abel L, Cooper AM, Notarangelo LD, Boisson-Dupuis S, Puel A, Sallusto F, Bustamante J, Tangye SG, Casanova JL. Impairment of IL-17 immunity to Candida and IFN-g immunity to Mycobacterium in humans with inherited RORgT deficiency. Science (Published online 10th July 2015)

Ma C, Wong N, Rao G, Avery D, Torpy J, Bustamante J, Okada S, Stoddard J, Deenick EK, Pelham S, Boisson-Dupuis S, Puel A, Kobayashi M, Arkwright P, Kilic SS, El Baghdadi J, Nonoyama S, Minegishi Y, Mahdaviani SA, Mansouri D, Bousfiha A, French M, Hsu P, Campbell D, Stormon M, Wong M, Adelstein S, Smart J, Fulcher D, Cook M, Phan TG, Stepensky P, Boztug K, Ikincioğullari A, Beier R, Ziegler J, Gray P, Picard C, Grimbacher B, Warnatz K, Holland S, Casanova JL, Uzel G, Tangye Sfg. Monogenic mutations differentially impact the quantity and quality of T follicular helper cells in human primary immunodeficiencies. J Allergy Clin Immunol (Published online July 8th 2015).

Wilson RP, Ives ML, Rao G, Lau A, Payne K, Kobayashi M, Arkwright PD, Peake J, Wong M, Adelstein S, Smart JM, French MA, Fulcher DA, Picard C, Bustamante J, Boisson-Dupuis S, Gray P, Stepensky P, Warnatz K, Freeman AF, Rossjohn J, McCluskey J, Holland SM, Casanova J-L, Uzel G, Ma CS, Tangye SG, and Deenick EK.  STAT3 is a critical cell intrinsic regulator of human unconventional T cell numbers and function. J Exp Med  212: 855-864. May 2015

AY Kreins, M Ciancanelli, S Okada, X-F Kong, N Ramirez-Alejo, SS Kilic, J El Baghdadi, S Nonoyama, S Alireza Mahdaviani, F Ailal, A Bousfiha D Mansouri, E Nievas, CS Ma, A Bernasconi, H Kuehn, J Niemela, J Stoddard, P Deveau, A Cobat, S El Azbaoui, A Sabri, R Halwani, A Grant, B Boisson, D Bogunovic, Y Itan, M Moncada-Velez, R Martinez-Barricarte, M Migaud, C Deswarte, L Alsina, D Kotlarz, C Klein, I Muller-Fleckenstein, B Fleckenstein, V Cormier-Daire, S Rose-John, C Picard, L Hammarstrom, A Puel, S Al-Muhsen, L Abel, D Chaussabel, S Rozensweig, Y Minegishi, SG Tangye, J Bustamante, J-L Casanova, and S Boisson-Dupuis. 2015 Human TYK2 deficiency: mycobacterial and viral infections without hyper IgE syndrome. Journal of Experimental Medicine. (in press).

D Butt, TD Chan, K Bourne, JR Hermes, A Nguyen, A Statham, LA O’Reilly, A Strasser, S Price, P Schofield, D Christ, A Basten, CS Ma, SG Tangye, TG Phan, VK Rao, and R Brink. FAS inactivation releases unconventional germinal center B cells that escape antigen control and drive IgE and autoantibody production. Immunity. 42: 890-902. May 2015

CS Ma and EK Deenick. Human T follicular helper (Tfh) cells and disease. Immunology and Cell Biology. 2014;  (in press)

LJ Berglund, DT Avery, CS Ma, L Moens, EK Deenick, J Bustamante, S Boisson-Dupuis, M Wong, S Adelstein, PD Arkwright, R Bacchetta, L Berzrednik, H Dadi, C Roifman, DA Fulcher, JB Ziegler, JM Smart, M Kobayashi, C Picard, A Durandy, MC Cook, J-L Casanova, G Uzel, and SG Tangye.  IL-21 Signaling via STAT3 primes human naïve B cells to respond to IL-2 to enhance their differentiation into plasmablasts. Blood. 122: 3940-3950. 2013

CS Ma, EK Deenick, M Batten, and SG Tangye. The origins, function and regulation of T follicular helper cells. Journal of Experimental Medicine. 209:1241-1253. 2012

CS Ma, DT Avery, A Chan, M Batten, J Bustamante, S Boisson-Dupuis, PD Arkwright, Y Minegishi, S Nonoyama, MA French, S Choo, JM Smart, J Peake, M Wong, P Gray, MC Cook, DA Fulcher, J-L Casanova, EK Deenick, and SG Tangye. Functional STAT3 deficiency compromises the generation of human T follicular helper cells. Blood. 2012; 119:3997-4008.

KL Randall*, SS-Y Chan*, CS Ma*, I Fung*, Y Mei, M Yabas, A Tan, PD Arkwright, A Al Suwairi, S Oswaldo Lugo Reyes, MA Yamazaki-Nakashimada, M de la Luz Garia-Cruz, JM Smart, C picard, S Okada, E Jouanguy, JL Casanova, T Lambe, RJ Cornall, S Russell, J Oliaro, SG Tangye, EM Bertram, and CG Goodnow. DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice. Journal of Experimental Medicine. 2011; 208:2305-20. *equal contribution

DT Avery*, EK Deenick*, CS Ma*, S Suryani, N Simpson. GY Chew, TD Chan, U Palendira, J Bustamante, S Boisson-Dupuis, S Choo, KE Bleasel, J Peake, MA French, D Engelhard, S Al-Hajjar, S Al-Muhsen, K Magdorf, J Roesler, PD Arkwright, P Hissaria, DS Riminton, M Wong, R Brink, DA Fulcher, JL Casanova, MC Cook, and SG Tangye. B-cell intrinsic signalling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans. Journal of Experimental Medicine. 2010; 207:155-171. *equal contribution

CS Ma, S Suryani, DT Avery, A Chan, R Nanan, B Santner-Nanan, EK Deenick, SG Tangye. Early commitment of naïve human CD4+ T cells to the T follicular helper (TFH) cell lineage is induced by IL-12. Immunology and Cell Biology. 2009; 87:590-600.

S Chaganti*, CS Ma*, AI Bell, D Croom-Carter, AD Hislop, SG Tangye and AB Rickinson. Epstein-Barr virus persistence in the absence of conventional memory B cells: IgM+IgD+ CD27+ B cells harbour the virus in X-linked lymphoproliferative disease patients. Blood. 2008; 112:672-679. *equal contribution

CS Ma, KE Nichols and SG Tangye. Regulation of cellular and humoral immune responses by the SLAM and SAP families of molecules. Annual Review of Immunology. 2007; 25:337-379.

CS Ma, S Pittaluga, DT Avery, NJ Hare, I Maric, AD Klion, KE Nichols, and SG Tangye. Selective generation of functional somatically mutated IgM+CD27+, but not Ig isotype-switched, memory B cells in X-linked lymphoproliferative disease. Journal of Clinical Investigation. 2006; 116:322-333.

CS Ma, NJ Hare, KE Nichols, L Dupre, MG Roncarolo, S Adelstein, PD Hodgkin and SG Tangye. Impaired humoral immunity in XLP is associated with defective IL-10 production by CD4+ T cells. Journal of Clinical Investigation. 2005; 115:1049-1059.

More Garvan Publications

Staff in the Group