Tuberculous lymphadenitis is the most frequent site of extrapulmonary tuberculosis. About 20% of all TBC cases in the US are extrapulmonary. From this group, about 40% are tuberculous lymphadentis [
1]. Detection of
M. tuberculosis is mainly via the innate immune system by extracellular or intracellular pattern recognition receptors (PRR) such as toll-like receptors (TLR) and nucleotide-binding oligomerization domain receptors (NOD) [
2‐
4]. Mutations in specific TLR genes were found to be associated with susceptibility to TBC [
5,
6].
Clinical relevance of mutations in the
NOD2 gene arises from their association with Crohn’s disease [
7‐
10]. In 2001, a link between mutations in the
NOD2 gene and Crohn’s disease was first established independently by two different groups [
11,
12]. However, the exact function of
NOD2 is still under debate [
13]. Besides Crohn’s disease, other disease entities seem to be related to mutations in the
NOD2 gene like GvHD [
14‐
16], acute septicemia [
17], spontaneous bacterial peritonitis in liver cirrhosis [
18,
19] and worsened outcome after intestinal transplantation [
20]. Mutations in the
NOD2 gene and an increased susceptibility for infectious diseases have been reported in the literature [
21].
NOD2 is also thought to be an important receptor in recognizing
M. tuberculosis, because on the one hand both the receptor and the pathogen are intracellular and on the other hand the cell wall of
M. tuberculosis contains peptidoglycan, which is one of the ligands of
NOD2[
22]. However, the role of
NOD2 in tuberculous lymphadenitis has not been studied yet. To this end a recent study has described a new SNP in the
NOD2 gene as a possible risk factor for pulmonary tuberculosis in the Chinese Han population [
23]. In another study it was reported that genes in the
NOD2 signaling pathway are associated with susceptibility to infections with
Mycobacterium leprae in China [
24].
Short bowel syndrome (SBS) and intestinal failure requiring long term home parenteral nutrition (HPN) are rare heterogeneous clinical conditions in which extensive parts of the intestine have been removed surgically. The main causes of short bowel syndrome in adults are Crohn’s disease, intestinal ischemia, volvulus, ileus, desmoid tumors and trauma [
25]. Recently we have described an increased frequency of
NOD2 mutations in SBS patients without underlying Crohn’s disease [
26]. Infections associated with intestinal failure requiring home parenteral nutrition are mainly catheter-related [
27,
28].