New study shows 14-3-3η proteins as diagnostic marker, disease indicator, and lymphoma predictor for primary Sjögren’s syndrome

Recent research published in the Archives of Iranian Medicine has reported a pivotal finding regarding 14-3-3η proteins and their role in primary Sjögren syndrome (PSS). The study revealed a significant elevation of these proteins in the serum of PSS patients, along with a connection between them and various markers predictive of lymphoma development in PSS patients. 

Kor and colleagues examined 57 patients diagnosed with PSS and 54 healthy volunteers. The study revealed a substantial elevation in serum levels of the 14-3-3η protein among PSS patients compared to the healthy control group (2.72 vs 1.73). Moreover, the research revealed significant associations between 14-3-3η protein levels and several indicators linked to PSS severity and potential lymphoma development. Notably, significant correlations were observed between 14-3-3η protein levels and parameters such as the EULAR Sjogren’s syndrome disease activity index group (β=0.385), hypocomplementemia (C3 or C4) (β=0.223) and purpura (β=0.252), all recognized as predictors of lymphoma in PSS patients. Furthermore, a significant correlation was established between the PSS disease activity score, ESSDAI, and 14-33η protein levels (β=0.496, 95% CI=0.079-0.244, P=0.0002). These findings underscore the potential of 14-3-3η proteins as valuable biomarkers for assessing disease activity and predicting lymphoma development in individuals affected by PSS. 

The 14-3-3 proteins represent a diverse group of phospho-serine/phospho-threonine-binding isoforms, each interacting with various protein categories such as phosphatases, kinases, transcription factors, and transmembrane receptors. Abnormal expression of these proteins is strongly linked to numerous malignant diseases, with 14-3-3 proteins able to modulate oncogenic proteins. Among the 14-3-3 isoforms, 14-3-3ζ protein stands out for its connection with cancers of the lung, breast, prostate, ovaries, and stomach. Additionally, it has been implicated in chemotherapy resistance and poor prognosis in diffuse large B-cell lymphoma and extranodal NK/T-cell lymphoma. This multifaceted role underscores the significance of understanding the nuanced interactions of 14-3-3 proteins in different malignancies and highlights their potential as therapeutic targets. 

The emerging role of 14-3-3η proteins in PSS presents a promising avenue for advancing diagnostic precision, monitoring disease activity, and predicting lymphoma development in affected individuals. As demonstrated by recent research, the elevated levels of 14-3-3η proteins in PSS patients underscore their potential as valuable biomarkers. By unraveling these associations, clinicians may be better equipped to identify, manage, and potentially reduce the risks associated with PSS and its complications. Continued investigation into the utility of 14-3-3η proteins could ultimately lead to improved patient outcomes and personalized approaches to managing this complex autoimmune disorder. 


Kor A, Yalçın M, Erten Ş, Maraş Y, Oğuz EF, Doğan İ, et al. 14-3-3η Proteins as a Diagnostic Marker, Disease Activation Indicator, and Lymphoma Predictor in Patients with Primary Sjögren Syndrome. Arch Iran Med. 2023 Oct 1;26(10):582–91. 

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