As our understanding of genetics increases, so does our awareness of the multitude of genetic diseases—many of which continue to be discovered to this day. While X-linked lymphoproliferative disease (XLP) isn’t necessarily new, having been first described in medical literature in 2006, researchers still lack a deep understanding about the disease. After all, only an estimated 100 people worldwide have been diagnosed. News Medical explains that researchers have recently been advancing research into XLP type 2 (or XLP-2). Through these insights, we may better conceptualize what XLP-2 is and how it can potentially be treated.
XLP-2 results from XIAP gene mutations. In particular, shares Dr. Subash Sad, one of the authors of the study published in PLOS Pathogens, XIAP mutations which inactivate the gene could cause immunodeficiency. But how?
To answer this question, the research team explored how XIAP altered T cell differentiation and memory in mice models. They infected the mice with bacteria to identify how inactive XIAP impacted T cells. The researchers found that the gene alterations led to a multitude of T cell changes which prevented the immune system from working properly. In particular, T cells stopped surviving as long and could not proliferate as well—meaning that memory T cells do not confer continued benefit against infections.
More research is needed into the underlying disease mechanisms. However, this study shows promise in advancing a deeper understanding of this disease.
What We Know About XLP-2
Also known as: XIAP deficiency
As described above, XLP-2 is a form of X-linked lymphoproliferative disease, a rare genetic disorder that causes the immune system to overreact to infections. Because it is inherited in an X-linked pattern, it predominantly affects boys. People with XLP-2 may have an overexaggerated response to the Epstein-Barr virus (EBV) that can be fatal. Other symptoms may vary from person-to-person but can include:
- A recurrent fever
- Enlarged spleen and liver
- Gastrointestinal, joint, and ocular inflammation
- Hypogammaglobulinemia (lower antibody levels)
- Low red and white blood cell and platelet counts
- Hemophagocytic lymphohistiocytosis
- Fever
- Skin rash
- Diarrhea
- Unintentional weight loss
- Swollen lymph nodes
- Jaundice (yellowing of the skin, eyes, and mucous membranes)
- Difficulty absorbing nutrients
- Organ damage
Not every person with XLP-2 needs a bone marrow transplant (or allogeneic hematopoietic stem cell transplant), but this can be a cure. There are also some treatments available such as biologics, immunosuppressants, antibiotics, steroids, and chemotherapy.
Learn more about XLP-2.
