In this study, PIDs were detected in 18% of AILD patients. In patients with AILD and PIDs, lower and upper respiratory tract infections were more frequent. Although immune dysregulation in patients with PID makes them prone to autoimmunity, to the best of our knowledge, there is no research on the prevalence of PID in AILD patients in the literature.
Previous data regarding the association of AILD with PID limited to studies that investigate the frequency of autoimmune diseases in PID cohorts. In these studies, AIH was reported at a range of 1.6–43.0% in different PID syndromes [17–21]. PBC was detected in %1.2 of patients with CVID . PSC accompanied various types of PIDs in children  and was present as high as % 45 of patients with hyper immunoglobulin M syndrome . The prevalence of PIDs in the general population is estimated to be 1:10.000 but may be more frequent in populations with common consanguineous marriage [25, 26]. As such, it is estimated that PID prevalence is relatively higher in Turkey, with 24% consanguineous marriage in 2008 [27–29]. This is the first study investigating the frequency of PIDs among AILD, and PIDs were found in 18% (15/82) of AILD patients, which was significantly higher than estimations for the general population.
Concomitant PID and AILD is a challenging diagnosis. Because of the changes in immunological parameters, such as autoantibody titers and Ig levels. There are several case reports emphasizing the difficulties in diagnosing AIH with standard diagnostic criteria due to low immunoglobulin levels in CVID patients [30–32]. Furthermore, Fukushima et al. suggested that some CVID cases reported as “non-B non-C hepatitis” who benefited from immunosuppressive therapy may have had AIH . Similarly, some cases were described in the literature as “chronic hepatitis” accompanying CVID , and those may actually be undiagnosed AIH patients with accompanying PID. In our study, seronegativity rates among AIH and PBC patients were higher in the PID group than in the group without PID; however, this difference remained statistically insignificant due to the low number of observations. On the other hand, the diagnosis of PIDs may be overlooked in AILD patients since the increased frequency of infection is attributed to immunosuppressive treatment. Indeed, most of the patients with PID were diagnosed during this study, except for four patients previously diagnosed with CVID.
We do not know the effects of underlying PIDs on the prognosis and course of AILD. The increased frequency of infections in cirrhotic AILD patients with PIDs may accelerate their transition from compensated to decompensated state. PIDs may further increase the risk of infection in liver transplant recipients. In this study, upper respiratory infections and pneumonia were more common in PID patients than without PIDs, while viral and fungal infection rates were similar. The predominance of bacterial infections rather than viral infections can be explained by the fact that most AILD patients with PIDs patients had antibody deficiencies. The effect of PID-associated infections could not be examined since patients with decompensated cirrhosis were excluded from the study. Additionally, there was no difference in the rates of compensated cirrhosis and treatment unresponsiveness between patients with and without PID. Nevertheless, it may be due to the small number of patients included in the study.
An important question arises on which AILD patients should be investigated for PIDs. The literature points out frequent or atypical infections, autoimmunity, lymphoproliferative diseases, family history, and parental consanguinity as warming factors to investigate PIDs in the general population . We suggest that at least AILD patients with a history of frequent or severe infections should be evaluated for the associated PIDs.
To the best of our knowledge, this study is the first study that investigates the frequency of PIDs in AILD. The significantly higher frequency of PIDs among AILD than the general population and the lack of awareness about investigating PIDs in AILD has been revealed. However, there are some limitations. First, this is a single-center study, and the number of patients, especially PSC patients, was limited. Therefore, besides infections, we could not identify other warning parameters for PIDs. Secondly, the impact of PIDs on the diagnosis and prognosis of AILD could not be defined. Lastly, genetic analysis and histopathological evaluation could not be performed in order to investigate the possible mechanisms of interaction between immunodeficiency and autoimmunity in the liver. Further research with larger patient samples from multiple centers is needed to evaluate the prevalence of PIDs and their clinical impacts on AILD. In addition, histopathological and genetic studies are needed to better understand immune dysregulation in AILD patients with PID. These studies not only will better characterize and classify AILD by facilitating diagnosis and predicting prognosis, but they can also pave the way for targeted therapy in AILD patients.