Chaidos Lab

Contact

Dr Aristeidis Chaidos

  • Consultant haematologist and honorary senior lecturer at the Hammersmith Hospital and Imperial College London
  • Expertise in multiple myeloma, lymphoma, and stem cell transplantation

+44 (0)20 3313 4017
a.chaidos@imperial.ac.uk

Areas of research

Myeloma functional heterogeneity in clinical drug resistance and residual disease

Myeloma heterogeneity is the single most important obstacle for optimal therapeutic targeting. A complex genetic landscape, epigenetic mechanisms and cues from tumour microenvironments shape the phenotypic and functional diversification of myeloma cells, which underpins drug resistance and later relapsed disease. Differential transcriptional profiles and gene expression regulatory mechanisms at diagnosis and residual disease provide insight into the biology of drug resistance and reveal novel disease vulnerabilities.

The lab is particularly interested in the biology of BCL2 family proteins. BCL2 inhibition is a promising targeted therapy for t(11;14) myeloma and a unique paradigm of treatment directed by genetics.

Myeloma kidney disease and MGRS

Myeloma kidney disease is a debilitating complication with a profound impact on treatment outcome and survival. Monoclonal Gammopathy of Renal Significance (MGRS) is a rare disease, where small amounts of highly nephrotoxic immunoglobulins or free light chains, produced by otherwise subclinical plasma cell clones, resulting in a bewildering array of renal histopathology and kidney disease.

The lab collaborates with Renal Medicine and Histopathology at Imperial to establish experimental vitro and vivo models of myeloma cast nephropathy and MGRS. We study the proinflammatory and profibrotic pathways induced by the nephrotoxic immunoglobulins and develop novel diagnostics and therapeutic strategies.

Citation

BibTex format

@article{Kousios:2019:10.1016/j.ekir.2019.05.014,
author = {Kousios, A and Duncan, N and Charif, R and Tam, FWK and Levy, J and Cook, HT and Pusey, CD and Roufosse, C and Chaidos, A},
doi = {10.1016/j.ekir.2019.05.014},
journal = {Kidney International Reports},
pages = {1342--1348},
title = {Autologous stem cell transplant for the treatment of type I crystal cryoglobulinaemic glomerulonephritis caused by monoclonal gammopathy of renal significance (MGRS)},
url = {http://dx.doi.org/10.1016/j.ekir.2019.05.014},
volume = {4},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cryoglobulins (CGs) are immunoglobulins that precipitate at temperatures below 37°C and dissolve again after rewarming. Cryoglobulinemia may be asymptomatic or cause end-organ damage by CG precipitation in small- to medium-sized blood vessels.1 In their seminal work, Brouet et al.2 classify cryoglobulinemias into 3 subgroups according to CG composition and clonality. In type II cryoglobulinemia there is a mixture of monoclonal IgM with rheumatoid factor activity and polyclonal IgG. In type III, CGs consist of polyclonal IgM and IgG.1 Type II and III cryoglobulinemias are also referred to as mixed cryoglobulinemias and are often caused by chronic hepatitis C infection and less frequently by autoimmune diseases or other viral infections (hepatitis B infection, HIV).3CGs in type I cryoglobulinemia are monoclonal Igs (MIg), also known as paraproteins, commonly IgG, IgM subtypes, or free light chains. The underlying pathological process is a plasma cell or B-cell lymphoproliferative disease, such as multiple myeloma (MM), Waldenström macroglobulinemia, chronic lymphocytic leukemia, or other B-cell non-Hodgkin lymphoma. However, in approximately 40% of symptomatic cases, the plasma cell or B-cell clone is too small to fulfill the diagnostic criteria of MM or overt lymphoma. The term monoclonal gammopathy of undetermined significance (MGUS) used for these cases is a misnomer, as the MIg causes disease regardless of the size and tumor burden.4 For cases with renal involvement, the International Kidney and Monoclonal Gammopathy Research Group introduced the term monoclonal gammopathies of renal significance (MGRS).5 The updated MGRS definition includes monoclonal gammopathies that cause renal disease but have low tumor burden and thus treatment from the hematological standpoint is not imminently indicated.6 These patients may have fewer than 10% plasma cells in bone marrow biopsy, smoldering myeloma, or low-grade lymphomas.7 MGRSs are not of undetermined significanc
AU  - Kousios,A
AU  - Duncan,N
AU  - Charif,R
AU  - Tam,FWK
AU  - Levy,J
AU  - Cook,HT
AU  - Pusey,CD
AU  - Roufosse,C
AU  - Chaidos,A
DO  - 10.1016/j.ekir.2019.05.014
EP  - 1348
PY  - 2019///
SN  - 2468-0249
SP  - 1342
TI  - Autologous stem cell transplant for the treatment of type I crystal cryoglobulinaemic glomerulonephritis caused by monoclonal gammopathy of renal significance (MGRS)
T2  - Kidney International Reports
UR  - http://dx.doi.org/10.1016/j.ekir.2019.05.014
UR  - http://hdl.handle.net/10044/1/70895
VL  - 4
ER  -
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