Abstract
To date, several germline mutations have been identified in the LRBA gene in patients suffering from a variety of clinical symptoms. These mutations abolish the expression of the LRBA protein, leading to autoimmunity, chronic diarrhea, B-cell deficiency, hypogammaglobulinemia, functional T-cell defects and aberrant autophagy. We review the clinical and laboratory features of patients with LRBA mutations and present five novel mutations in eight patients suffering from a multitude of clinical features.
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Contribution
O.K. and H.A. performed experiments, analyzed results, made the figures, and wrote the paper; M.F. analyzed results; K.K., M.M, and J.C. performed experiments and analyzed results; H.A., Z.C., I.M., and M.E. performed clinical sampling and; A.A., N.R., R.G. and L.H. designed the research and edited the paper.
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This work was supported by the Jeffrey Modell Foundation and the Swedish Research Council.
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The authors declare no competing financial interests.
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Multiple Choice Questions
Multiple Choice Questions
Somatic mutations in LRBA have been linked to:
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1.
Chronic diarrhea
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2.
Immune thrombocytopenic purpura
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3.
Autoimmune hemolytic anemia
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4.
Breast cancer
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5.
Hypogammaglobulinemia
In LRBA deficiency, B-cell characteristics most commonly include:
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1.
An increased proportion of switched memory B-cells
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2.
A decreased proportion of switched memory B-cells
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3.
Normal autophagic function
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4.
Normal B-cell proliferation
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5.
Normal B-cell differentiation
Regarding mutations resulting in LRBA, which of the following statments is correct:
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1.
Only fragment deletions result in LRBA deficiency
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2.
Only nonsense mutations result in LRBA deficiency
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3.
Only mutations in exon 30 result in LRBA deficiency
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4.
Multiple mutations are necessary to result in LRBA deficiency
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5.
A single homozygous mutation may result in LRBA deficiency
LRBA is a:
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1.
Cell-surface receptor protein
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2.
Expressed in lymphoid cells only
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3.
Expressed in neural cells only
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4.
Expressed in B-cells only
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5.
Cytosolic protein
Regarding plasma cells, which of the following is correct :
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1.
Do not have autophagic activity
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2.
Have high autophagic activity
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3.
Lose their endoplasmic reticula during differentiation
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4.
Do not express autophagy-related proteins
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5.
Have a very low level of autophagy substrate SQSTM1 protein
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Alkhairy, O.K., Abolhassani, H., Rezaei, N. et al. Spectrum of Phenotypes Associated with Mutations in LRBA . J Clin Immunol 36, 33–45 (2016). https://doi.org/10.1007/s10875-015-0224-7
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DOI: https://doi.org/10.1007/s10875-015-0224-7
Keywords
- Primary immunodeficiency disorders (PID)
- lipopolysaccharide responsive beige-like anchor protein (LRBA)
- common variable immunodeficiency (CVID)
- autoimmune disease (AID)
- chronic diarrhea (CD)
- hypogammaglobulinemia (HGG)
- organomegaly (OM)
- regulatory T-cells (Treg)
- cytotoxic T-lymphocyte-associated protein 4 (CTLA4)
- autophagy
- apoptosis