Immunogenetics and Immunotherapy team

We focus on two main areas of immunological research - Immunogenetics and Immunotheraphy.

The Immunogenetics and Immunotherapy team has focused on the study of the immune system in humans and other organisms to investigate pathophysiology and physiology in health, immunological disorders including immunodeficiency and characteristics in vitro, in vivo and in situ. This team also has aimed to explore applications in a clinical environment, immunotherapy, diagnostic immunology, immunogenetics, multi-omics technologies, gene-knockout/in models and bioinformatics.

Illustration image of Immunogenetics: Gene hunting in unsolved primary immunodeficiency.
Immunogenetics: Gene hunting in unsolved primary immunodeficiency. Photo: Hassan Abolhassani

Our lab is one of the main international reference referral centers for molecular diagnosis of unsolved patients with complicated immunologic disorders mainly primary antibody deficiency and wa have been involved in some of the main human genetic disorder discoveries including TACI, LRBA, IFIH1, CLEC16A, RAC2, CD27 and CD70 deficiencies. Our team has continuously targeted toward diagnostic and therapeutic challenges of inborn immune system disorders, particularly with B cell pathogenesis. Using a multidisciplinary approach, we have developed an advanced multi-omics pipeline to discover and validate novel immune-related gene defects. Patients with primary immunodeficiency present different infectious and non-infectious complications including autoimmunity, inflammatory disorders, allergies and cancers. Therefore, with understanding the mechanisms underlying these diseases, we can help not only the patients and their families but also a wide variety of unsolved chronic and common disorders with a high global burden.

Illustration of Advance newborn screening of primary immunodeficiency.
Advance newborn screening of primary immunodeficiency. Photo: Hassan Abolhassani

Another main project of our team is population-based newborn screening for primary immunodeficiency which enables the early identification of asymptomatic infants with a range of severe diseases, for which effective treatment is available and where early diagnosis and intervention prevent serious sequelae. In line with our recent pilot study on screening 89,462 newborn infants using the number of T-cell receptor excision circle (TREC)/kappa-deleting recombination excision circle (KREC) copies and our estimated incidence of SCID at the same level as in other studies (around 1:50,000), we could successfully convince the Swedish health policymaker to establish national newborn screening available for all neonates in 2019, starting on August 1st using our own TREC/KREC assay. Our kits for the newborn SCID screening are now also used in the national screening program in Germany, Poland, Switzerland, Iceland and the Netherlands.  Moreover, we recently developed a newborn screening method based on multiplex protein profiling for parallel diagnosis of innate immunodeficiencies affecting the complement system and phagocytic disorders as well as RNA based method using samples from dried blood spot specimens for early diagnosis of hypogammaglobulinemia.

Illustration of Genetically modified lactobacilli for the treatment of human disorders.
Genetically modified lactobacilli for the treatment of human disorders. Photo: Yin Lin

Moreover, passive administration of antibodies represents the therapy of choice for mucosal infections, particularly in children and immunocompromised individuals and during the past two decades, oral administration of polyclonal antibodies against selected enteric pathogens has been employed successfully. However, the production and purification of these antibodies is costly and therefore, efforts have been made to develop new methods for the production of monoclonal antibodies or antibody fragments employing plant, yeast and bacterial systems. An attractive idea is to use lactobacilli as vectors for in situ delivery of antibody fragments and other therapeutic molecules at mucosal surfaces. Lactobacilli are Gram-positive bacteria with a long history of safe use in food fermentation and preservation. They are also a significant component of the naturally occurring gastrointestinal and vaginal microbiota. The desired genes can be integrated into the bacterial genome, creating food-grade, genetically modified lactobacilli. The modified lactobacilli can be freeze-dried or spray-dried and subsequently incorporated in capsules or food products. We have previously shown that genetically modified lactobacilli delivering antibody fragments against HIV, S. mutans, rotavirus, and C. difficile are protective in animal models. In addition, lactobacilli can be used to deliver a range of therapeutic molecules in the gastrointestinal tract such as cytokines, antimicrobial peptides and glucacon-like peptides.

Illustration of Passive immunotherapy against SARS-CoV-2 infection.
Passive immunotherapy against SARS-CoV-2 infection. Photo: Hassan Abolhassani

 Last but not least, the team is actively involved in the research toward COVID-19 pandemic to develop passive immunotherapy against SARS-CoV-2 with the help of donated blood samples from recovered COVID-19 patients. With experimental and computational work, we plan to optimize, produce and test human polyclonal and monoclonal antibodies for the treatment of patients with COVID-19 (EU consortium project- ATAC PROJECT). Moreover, we investigate the impact of the COVID-19 pandemic on patients with primary immunodeficiency and identification of the protective measures for this vulnerable group of patients.

Research team leaders

Harold Marcotte

Researcher
H5 Department of Laboratory Medicine

Group members

External funding

Swedish Research Council, EU, Erling-Persson, ALF

Teaching assignments

BMA, study programme in medicine, study programme in medicine

Selected publications

Development of passive immunity against SARS-CoV-2 for management of immunodeficient patients-a perspective.
Hammarström L, Abolhassani H, Baldanti F, Marcotte H, Pan-Hammarström Q
J. Allergy Clin. Immunol. 2020 07;146(1):58-60

Current genetic landscape in common variable immune deficiency.
Abolhassani H, Hammarström L, Cunningham-Rundles C
Blood 2020 Feb;135(9):656-667

Noncoding RNA transcription alters chromosomal topology to promote isotype-specific class switch recombination.
Rothschild G, Zhang W, Lim J, Giri PK, Laffleur B, Chen Y, et al
Sci Immunol 2020 02;5(44):

Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common TYK2 missense variant.
Boisson-Dupuis S, Ramirez-Alejo N, Li Z, Patin E, Rao G, Kerner G, et al
Sci Immunol 2018 12;3(30):

Predictive markers for humoral influenza vaccine response in patients with common variable immunodeficiency.
Gardulf A, Abolhassani H, Gustafson R, Eriksson LE, Hammarström L
J. Allergy Clin. Immunol. 2018 12;142(6):1922-1931.e2

Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency.
Abolhassani H, Edwards ES, Ikinciogullari A, Jing H, Borte S, Buggert M, et al
J. Exp. Med. 2017 01;214(1):91-106

Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency.
Bronson PG, Chang D, Bhangale T, Seldin MF, Ortmann W, Ferreira RC, et al
Nat. Genet. 2016 11;48(11):1425-1429

Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection.
Tokuhara D, Álvarez B, Mejima M, Hiroiwa T, Takahashi Y, Kurokawa S, et al
J. Clin. Invest. 2013 Sep;123(9):3829-38

Impact of Down syndrome on the performance of neonatal screening assays for severe primary immunodeficiency diseases.
Verstegen RH, Borte S, Bok LA, van Zwieten PH, von Döbeln U, Hammarström L, et al
J. Allergy Clin. Immunol. 2014 Apr;133(4):1208-11

The dog as a genetic model for immunoglobulin A (IgA) deficiency: identification of several breeds with low serum IgA concentrations.
Olsson M, Frankowiack M, Tengvall K, Roosje P, Fall T, Ivansson E, et al
Vet. Immunol. Immunopathol. 2014 Aug;160(3-4):255-9

Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia.
Bolze A, Mahlaoui N, Byun M, Turner B, Trede N, Ellis SR, et al
Science 2013 May;340(6135):976-8

Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR.
Borte S, von Döbeln U, Fasth A, Wang N, Janzi M, Winiarski J, et al
Blood 2012 Mar;119(11):2552-5

Selective IgA deficiency in autoimmune diseases.
Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al
Mol. Med. 2011 ;17(11-12):1383-96

Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency.
Ferreira RC, Pan-Hammarström Q, Graham RR, Gateva V, Fontán G, Lee AT, et al
Nat. Genet. 2010 Sep;42(9):777-80

Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseases.
, Rioux JD, Goyette P, Vyse TJ, Hammarström L, Fernando MM, et al
Proc. Natl. Acad. Sci. U.S.A. 2009 Nov;106(44):18680-5