Prof. Menno van Zelm, Professor, Monash University

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Prof. Menno van Zelm, Professor, Monash University

Biosketch:

Professor Menno van Zelm heads the Allergy and Clinical Immunology Laboratory in the Department of Immunology and Pathology at the Alfred Research Alliance (ARA) precinct. Menno van Zelm performed his PhD studies at the Erasmus MC in Rotterdam, the Netherlands on "B cell development and primary antibody deficiencies" under supervision of Jacques van Dongen and Mirjam van der Burg. These studies resulted in new insights on stepwise human B cell differentiation in bone marrow, and on homeostatic and antigen-induced B cell proliferation with the newly developed KREC assay. Furthermore, Menno described the first antibody-deficient patients with CD19 gene defects. Between 2005 and 2007, he spent 18 months in the laboratory of Kees Murre at the University of California San Diego (UCSD) on the structural organization of the Ig heavy chain locus in developing B cells.

In 2008, Prof van Zelm returned to Rotterdam for postdoctoral studies on CD19-complex deficiencies and he identified the first CD81 deficiency. From 2009, he headed a research group in the Erasmus MC (since 2013 as Associate Professor and since 2022 as Full Professor), and works on the regulation of Ig repertoire formation in precursor-B-cell development and the generation of memory B cells and plasma cells. Most studies involve human material to allow direct translation to patient care. Current disease models include antibody deficiencies, vacination for viral infections (COVID19, influenza) and IgE-mediated allergies. He moved to Monash University in 2015.

Prof van Zelm has received multiple personal grants since 2009, including a Veni Fellowship from the Netherlands Organisation for Scientific Research (NWO). In 2010, he received the Heineken Young Scientists Award from the Royal Netherlands Academy of Sciences (KNAW). Prof van Zelm is an academic editor for the international journals PLoS One, Frontiers in Immunology, and Immunotherapy Advances. He is chair of the IUIS Nomenclature committee and incoming president of the Human Cell Differentiation Molecules (HCDM) organisation that assigns new CD nomenclature and currently evaluates expression patterns of previously assigned CD markers in the CDMaps project.

Title of Talk:

"Identification of novel biomarkers for allergen immunotherapy through single-cell RNA sequencing"

Abstract:

Sublingual immunotherapy (SLIT) for grass pollen allergy can modify the natural history of allergic rhinitis and is associated with increased allergen-specific IgG4 . IgG4 competitively inhibits functional IgE on the surface of effector cells, such as mast cells and basophils, from binding to allergens. To further understand the important role memory B-cell (Bmem) responses play in mediating the beneficial effects of SLIT, we assessed changes in allergen-specific Bmem subsets induced by SLIT for grass pollen allergy.

Methods: Blood samples were collected twice outside the pollen season from twenty-seven patients with sensitization to ryegrass pollen (RGP; Lolium perenne) and seasonal rhinoconjunctivitis. Thirteen received 4-month pre-seasonal SLIT for grass pollen allergy, and 14 received standard pharmacotherapy only. Single-cell RNA sequencing was performed on FACS-purified Lol p 1-specific Bmem before and after SLIT from four patients, and significant genes were validated by flow cytometry on the total cohort.

Results: Four months of SLIT increased RGP-specific IgE and IgG4 in serum and induced two Lol p 1-specific Bmem subsets with unique transcriptional profiles. Both subsets had upregulated expression of beta 1 integrin ITGB1 (CD29), whereas IGHE (IgE), IGHG4 (IgG4 ), FCER2 (CD23), and IL13RA1 were upregulated in one subset. There was an increase in the proportion of Lol p 1+ Bmem expressing surface IgG4 , CD23, and CD29 after SLIT.

Conclusions: A clinically successful 4 months course of SLIT for grass pollen allergy induces two transcriptionally unique Bmem fates. Associated changes in surface-expressed proteins on these Bmem subsets can be used as early biomarkers for treatment effects.