Dr. Khass – An Update on Travelling Lighter with Arthritis

Dr. Khass – An Update on Travelling Lighter with Arthritis

Mohamed Khass, PhD, is a post-doctoral fellow in the Division of Clinical Immunology and Rheumatology at the University of Alabama. A strong research background in numerous areas including pharmacology, biochemistry, genetics, microbiology and immunology has not only created a researcher capable of unique insights from a multidisciplinary perspective, but has set Dr. Khass apart as a researcher to watch. The ANRF grant received as a 2019-2020 ANRF scholar was certainly a contributing factor in this researcher’s career trajectory. He firmly believes that the ANRF grant facilitated his promotion at the University of Alabama to assistant professor.

Increasingly interested in immunology, Dr. Khass had his eureka moment when he observed an interesting phenomenon – B cells (cells that play a significant role in our immune systems) that lacked a specific signaling molecule on their surface were linked to increased bone fragility. Bone biology and the interplay between early B cell and skeletal homeostasis became the focus of Dr. Khass’ research.  “The focus of my research is the mechanism of crosstalk between early B lineage cells and bone forming cells.”

B cells have surface molecules that allow them to recognize foreign cells. These signaling molecules are known as B cell receptors (BCRs), which allow the B cells to bind to a specific antigen (a toxin or substance capable of producing an immune response, in other words the enemy!). As these B cells develop and mature the body decides whether they should survive and multiply or whether they should be destroyed. If the B cells lack the BCRs necessary to identify their targets or if the BCRs are defective the B cell will not survive.

During the early stages of B-cell development, one such receptor molecule is the pre-B-cell receptor (pre-BCR). If this signaling molecule is not functioning correctly our bones are simply not as strong. Dr. Khass determined that a portion of this pre-BCR called the surrogate light chain (SL), if absent or malfunctioning, could influence bone health and the development of arthritis as we age. So ironically, we need a light chain to make our bones heavy enough!

In the previous twelve months Dr. Khass’ data has demonstrated that mice deficient in both immunoglobulin joining genes and preB cell product, lambda 5, have signs of accelerated arthritis. Samples from the joints of these mice showed inflammatory arthritis as early as two months of age. The findings suggesedt that collaborative absence of B cells and immunoglobulin protein lambda 5 could lead to bone and joint inflammation earlier in life. Using Different mouse models, Dr. Khass and his team evaluated bone and joint integrity during development and upon aging, concluding that the absence of lambda 5 leads to premature bone loss affecting joint.  The data also showed that this phenotype is more prominent in female than male mice, resembling the natural history of rheumatic disease in humans.

“The data we obtained indicate a novel finding. We are documenting an age-associated decrease in expression of lambda 5 seen in both mice and humans that affects both immune and skeletal systems. Absence of lambda 5 with aging leads to reduced bone mass and accelerated osteoporosis that influence joints.”

Currently the laboratory is in the process of dissecting the mechanistic details behind the pathophysiology of these rheumatic changes. “A second manuscript revealing our finding is in process of being published delineating the importance of our findings. This work is the fruit of the generous and continuous support of ANRF and all its team.”

These findings could form the basis for the identification and introduction of new diagnostic and therapeutic targets for rheumatic diseases using immune system products.  At the start of this grant Dr. Khass hoped that with continued support from ANRF and his home institution he can shed light on the mechanisms by which early B cells affect joint and bone homeostasis. He has achieved that goal, helping those with arthritis to move and live lighter.

ANRF
Article Author
Arthritis National Research Foundation
arthritisresearch@curearthritis.org

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. Writing articles about the patients affected and the science being done to find a cure shows why we need to come together to #CureArthritis!

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