# Current Challenges in _Yersinia_ Diagnosis and Treatment
## 9 Diagnosis
IgM antibodies are markers of the acute phase of yesriniosis, which are synthesized within the first week of infection and reach peak levels in the second week (Table 4). They decline to normal levels within 3-6 months. In rare cases, such as IgM deficiency, antibodies against _Yersinia_ in this class are not synthesized [153]. The lack of IgM synthesis is rare (less than 300 cases described in the literature) and is defined as an IgM concentration level lower than 0.40 g/L [154]. Selective IgM deficiency (sIGMD) results from immune deregulation associated with a severe lack of B cell differentiation [155]. IgA antibodies are the most important markers of reactive arthritis. They increase at the onset of yesriniosis and decrease after infection [151]. However, they may persist for 14 to 16 months after the first symptoms, especially in the cases where development of reactive arthritis or chronic enteritis occurs. If the course of yesriniosis is typical (uncomplicated), they can be detected up to five months after infection. IgA is synthesized in the intestine at a rate of 3-5 g/day and initially appears in the blood at a concentration of 2 to 3 mg/mL [156; 121]. IgA is essential for the immunological protection of mucosal surfaces in the respiratory and gastrointestinal tract [157]. IgA antibodies to YOPE (23 kDa), YOPD (35 kDa), and YOPB (41 kDa) occur in chronic enteritis, whereas antibodies to YOPD develop in 90% of cases of reactive arthritis. IgA is not synthesized in selective IgA de ficiency, the most common type of primary immunodeficiency [158]. However, reduced or absent IgA in the blood may accompany normal levels of IgM and IgG, especially in children over four years of age [158]. IgA antibodies are most important in diagnosing reactive arthritis [151]. In chronic yessiniosis, elevated IgA levels persist with increasing IgG. Interestingly, all patients with positive IgG and IgA against two or more YOPs develop chronic symptoms, often leading to persistent _Yersinia_ infection [159]. Analysis of the IgG subclasses (IgG1, IgG2, IgG3, IgG4) in patients with arthritis (n = 35) and uncomplicated yersiniosis (n = 49) showed that in patients with gastritis, the prevalence of IgG2 antibodies to _Yersinia_ Yop proteins increased with age and was the highest after the age of 40. The IgG1 corresponding to Yop proteins and IgG3 to LPS were diagnosed more frequently in children than adults [160]. It is worth emphasizing that any antibody analysis should be interpreted cautiously, as cross-reactivity has been observed between _Yersinia_ and _Borrelia burgdorferi_, _Brucella_, _Chlamydia pneumoniae_, _Bartonella_, and _Rickettsia_. In addition to reactivity with specific pathogens, they may cross-react with thyroid-stimulating immunoglobulin (TSH) [161]. Serological tests are usually performed in most laboratories, but the presence of antibodies is not part of the diagnostic criteria for yersiniosis. Antibody testing can be used as a screening tool to detect the current infection, but further confirmation is required by another test, most often by stool culture. Unfortunately, the commonly used procedures are expensive and time-consuming, and therefore are rarely used in standard microbiological laboratories [148]. Therefore, scientists and technologists are looking for procedures that will allow for more accessible isolation of these bacterial enteropathogens. Recently, several multiplex molecular tests have been developed that combine various methods (microscopy, antigen testing, culture, and real-time PCR) and detect Yersinia and other gastrointestinal pathogens (up to 20) directly from clinical stool samples within one hour. One of the useful tools for rapid and sensitive diagnosis, distinguishing three pathogenic Yersinia groups, is the multiplex PCR method. It enables the differentiation of three pathogenic _Yersinia_ groups: highly pathogenic _Y. enterocolitica_ (including serotype O8), low pathogenic _Y. enterocolitica_, and _Y.