Human BCL10 laboratory

We are the reference laboratory for Human BCL10 Deficiency. BCL10 deficiency is an autosomal recessive primary immunodeficiency responsible of combine immunodeficiency. Our laboratory has reported the four patients described to date due to this deficiency:

Table summarizes the main genetic, clinical, immunological and cellular features comparing both BCL10-deficient patients:

Patient	Mutation /Protein expression	Consanguinity	Lymphocyte phenotype / Immunoglobulin levels	Cellular response	Main clinical features	Treatment
P1	g.85741978C>T (GRCh37.p13) IVS1+1G>A Homozygous. No protein expression.	Consanguineous parents	Normal total numbers of T and B cells but mostly with a naïve phenotype. Reduction of Tregs Hypogammaglobulinemia. (IgG, IGA and IgM)	Normal responses to TLR1/2, TLR4, TLR2/6, and Dectin-1 signaling by MDMs and MDDCs. Impaired TLR4, TLR2/6, and Dectin-1 signaling in fibroblasts. Blocked T-cell proliferation in response to TCR stimulation.	6mo: Gastroenteritis, otitis and respiratory infections. 8mo: Viral infection (flu A and B, adenovirus; respiratory syncytial virus (RSV)); acute secondary respiratory failure, oral candidiasis and diaper dermatitis. 13mo: Prolonged diarrhea (Campylobacter jejuni). 18mo: Diarrhea. Active chronic colitis. 2y 5mo: Acute gastroenteritis (adenovirus) and respiratory infection (RSV). 2y 8mo: Diarrhea (adenovirus). Chronic non-specific colitis. 2y 10mo: Seizures and status epilepticus. Secondary diffuse leukoencephalopathy. 3y 4mo: Diarrhea (Clostridium difficile). Dizziness, disorientation and generalized weakness with focal abnormal movements. Suspected encephalitis. Died due to respiratory failure.	Deceased [1]
P2	g.85270702G >A (GRCh38.p12) p.R88X Homozygous. No protein expression.	Consanguineous parents	Normal total numbers of T and B cells but mostly with a naïve phenotype. Hypogammaglobulinemia (IgG, IGA and IgM)	Impaired TLR4, TLR2/6, and Dectin-1 signaling in fibroblasts.	1mo: Flare of the BCG scar with increased erythema and swelling 6mo: Severe viral lower respiratory tract infection and palatal ulcers. 8mo and 10mo: lower respiratory tract infections not requiring hospitalisation. 11mo: Acute onset respiratory distress (Mycobacterium tuberculosis and no evidence fungal infection).	HSCT [3]
P3	g.85270779A>T (GRCh38.p12) p.K63X Homozygous, No protein expression.	Consanguineous parents	Lymphocytosis. Absence of memory T and B cells. Reduction of NK, gdT, Tregs, and T_FH cells. Hypogammaglobulinemia (IgM)		1yo: Hospitalized due to pneumonia (bacterial).	HSCT [2]
P4	NM_003921.5: c.271A>C pT91P Homozygous, protein expression: not available	Consanguineous parents	Normal total numbers of T and low B cells numbers Hypogammaglobulinemia (IgG)	Blocked T-cell proliferation in response to TCR stimulation.	1mo: Scalp dermatitis with involvement of the trunk and axilla. Recurrent ear infections. Recurrent respiratory infections: Pneumocystis jiroveci, adenovirus, acute respiratory distress syndrome (ARDS), bilateral pneumonia requiring ventilatory support. Unable to sit upright at 7mo.	HSCT (Deceased) [4]
P5	g.85736522C>T (GRCh37.p13), p.R42H Homozygous, Low levels of protein expression.	Consanguineous parents	Normal total numbers of T and slight low B cells numbers Hypogammaglobulinemia (IgG and IgM)	Impaired TLR4, TLR2/6, and Dectin-1 signaling in fibroblasts.	Severe eczema; developmental delay; positive respiratory culture for Moraxella catarrhalis; pneumonia due to Klebsiella pneumoniae andskin infection due to Methicillin-resistant Staphylococcus aureus, Mollosum contagiousum and Micosporum canis.	Monthly IVIG and low potency steroid. No transplanted

1. Torres JM, Martinez-Barricarte R, Garcia-Gomez S, Mazariegos MS, Itan Y, Boisson B, et al. Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity. J Clin Invest. 2014;124:5239–48.

2. Garcia-Solis B, Van Den Rym A, Pérez-Caraballo JJ, Al-Ayoubi A, Alazami AM, Lorenzo L, et al. Clinical and Immunological Features of Human BCL10 Deficiency. Front Immunol. 2021;12:786572.

3. Van Den Rym A, Taur P, Martinez-Barricarte R, Lorenzo L, Puel A, Gonzalez-Navarro P, et al. Human BCL10 Deficiency due to Homozygosity for a Rare Allele. J Clin Immunol. Netherlands; 2020;40:388–98.

4. Al-Tamemi S, Alhinai Z, Al-Rahbi N, Al-Abdawani R, Al-Yazidi L, Al-Shekaili J, et al. BCL10 loss-of-function novel mutation leading to atypical severe combined immunodeficiency. Clin Immunol. United States; 2022;241:109067.

If you have a patient with a suspect of BCL10 deficiency you can contact with us ( perezdediegor@gmail.com / rebeca.perez@idipaz.es ) and we will characterize him/her.