CVID-associated TACI mutations affect autoreactive B cell selection and activation
Authors: Tineke Cantaert
Laurence Menard
Natalia Martinez-Pomar
Neil Romberg
Bodo Grimbacher
Eric Meffre
Manmeet Virdee
Tuure Kinnunen
David Saadoun
Maurizio Gentile
Charlotte Cunningham-Rundles
Nicolas Chamberlain
Raif Geha
Yen Shing Ng
Henner Morbach
Andrea Cerutti
Nuria Matamoros
Rima Rachid
Journal: Journal of Clinical Investigation (2013)
Discipline: CLINICAL MEDICINE
Keywords: Common variable immune deficiency; CVID; TACI mutations; B cell activation; immune tolerance

Abstract:  Common variable immune deficiency (CVID) is an assorted group of primary diseases that clinically manifest with antibody deficiency, infection susceptibility, and autoimmunity. Heterozygous mutations in the gene encoding the tumor necrosis factor receptor superfamily member TACI are associated with CVID and autoimmune manifestations, whereas two mutated alleles prevent autoimmunity. To assess how the number of TACI mutations affects B cell activation and tolerance checkpoints, we analyzed healthy individuals and CVID patients carrying one or two TACI mutations. We found that TACI interacts with the cleaved, mature forms of TLR7 and TLR9 and plays an important role during B cell activation and the central removal of autoreactive B cells in healthy donors and CVID patients. However, only subjects with a single TACI mutation displayed a breached immune tolerance and secreted antinuclear antibodies (ANAs). These antibodies were associated with the presence of circulating B cell lymphoma 6-expressing T follicular helper (Tfh) cells, likely stimulating autoreactive B cells. Thus, TACI mutations may favor CVID by altering B cell activation with coincident impairment of central B cell tolerance, whereas residual B cell responsiveness in patients with one, but not two, TACI mutations enables autoimmune complications. 

Retracted: No

PubPeer comments:
 (a) The authors in Definition 1 quoted the notion of q-rung orthopair fuzzy set and called the value $$pi_A(x) = bigg(mu_A(x)^q +  u_A(x)^q - mu_A(x)^q u_A(x)^q bigg)^{1 q}$$ the indeterminacy degree of $x$ in $A$. The quoted paper is Ref[39]. However, such a definition of u201cthe indeterminacy degreeu201d did not appear in Ref[39]. (b) The authors introduced in Definition 2 the notion of **q-rung picture fuzzy numbers**, which was proposed in Ref[23], and in Definition 3 proposed **a new ranking method** for q-rung picture fuzzy numbers. However, there was a ranking method in Ref[23] for q-rung picture fuzzy numbers. This paper and Ref[23] have shared authors. The new ranking method in this paper **was presented directly without any justification and was not compared with the ranking method in Ref[23].** See also the comment for Ref[23] on https: pubpeer.com publications 310BD3ABF66D93F57949DE5313462B (c) The authors in Definition 4 introduced the notions of Dombi T-norm and T-conrom from Ref[30], where the T-conorm is given in eq.(4) as $$D^c(x,y) = 1-D(x,y)$$ It is clear that the mapping defined by $D^c(x,y)$ is not Dombi T-conorm in the sense of Ref[30]. (d) The authors defined some operations in Definition 5 for q-rung picture fuzzy numbers. However, the $otimes$ operation is not sound because $$(0,1,0)times (0,0,1) =(0,1,1)$$ which is not a q-rung picture fuzzy number. (e) The **scalar multiplication defined in Definition 5 is also not sound** according to the numerical example presented for the case $q=2$ on https: pubpeer.com publications FAD84F5548FDDD389DC52131F79A96 As a consequence, the series of aggregation operators defined in this paper are not sound because they rely on the operations defined in Definition 5. ![file] ,