This editorial introduces a topical collection emerging from the Second SUMMIT Conference and the GROWTH research group session, focused on bridging science and innovation in translational medicine. Nevertheless, translating biomedical discoveries into clinical practice remains a critical bottleneck in healthcare progress. Furthermore, despite decades of research investment, the gap between basic science findings and patient care remains wide across various medical specialties. In this collection, we address fundamental questions about how scientific breakthroughs can be more effectively channeled into diagnostic improvements, therapeutic innovations, and clinical applications – all of which require interdisciplinary efforts. Key themes include the refinement of diagnostic methodologies, the development of targeted therapeutic approaches, and the systematic evaluation of translational pathways from the bench to the bedside. Together, the collected contributions offer insights into more effective frameworks for translational research while highlighting the complex organizational, technical, and conceptual barriers that must be overcome to achieve truly innovative healthcare solutions.

translational medicine, immunopathology, precision diagnostics, cytokine profiling, infectious diseases, innovative therapies

Precision medicine faces mounting challenges as we cope with complex global health threats. Furthermore, the gap between basic science findings and actual patient care remains wide, despite decades of investment in research. This special issue addresses some of these problems directly, bringing together researchers from rheumatology, infectious diseases, pediatrics, neurology, reproductive medicine, and immunology who are working to translate scientific breakthroughs into clinical impact.

The role of the immune system in some diseases continues to alarm us. Multiple papers in this issue examine how cytokines, such as IL-6, IL-17, and IL-33, drive a range of conditions – from seasonal allergies to devastating autoimmune diseases. What is particularly striking is how the same molecular players appear across such different diseases, suggesting we might be missing fundamental connections. The gene expression work and cytokine profiling studies offer some answers, though they also raise new questions about why certain patients respond so differently to the same triggers, rendering accurate diagnosis a persistent and real challenge. Among many examples, the comparative studies on tuberculosis testing and autoantibody detection highlight the significant room for improvement in our current methods. Anyone who has worked with IGRA tests or attempted to standardize ANA results is familiar with the frustrations these researchers are addressing. The analysis of preeclampsia risk factors and cancer studies adds another layer, showing how systemic inflammation complicates diagnosis across completely different clinical scenarios.

Furthermore, the COVID-19 shadow still looms large over clinical practice. The post-pandemic studies collected here reveal ongoing health effects we are only beginning to understand. The reactions to COVID-19 vaccines in children and MIS-C neurological complications are particularly sobering reminders of how much we underestimated this virus initially. The pandemic preparedness strategies feel both necessary and insufficient – we know another crisis is coming, but are we ready? (Mahroum et al. 2022). Furthermore, the recently established concept of post-COVID-19 syndrome (long COVID) reminded us of an array of relatively vaguely described postinfectious syndromes following viral infections, requiring our attention and better understanding (Choutka et al. 2022).

On the treatment front, some genuinely exciting developments are emerging. CAR-T cell therapy moving into autoimmune diseases represents a major shift in thinking. The bispecific antibody work shows similar promise, although the complexity of these approaches raises questions about their real-world implementation. The studies on immunomodulation for infertility and cardiometabolic intervention strategies suggest that we are finally moving beyond one-size-fits-all approaches, albeit slowly. These contributions reflect where biomedical research stands today – making genuine progress while acknowledging the areas where we still have much to learn. The path from bench to bedside remains long and uncertain, but work like this gives reason for cautious optimism about more personalized and effective therapeutic opportunities.

Rheumatology and the world of systemic autoimmune rheumatic diseases have undergone a significant transformation over recent decades. From a field of vaguely defined entities with very limited treatment options, both diagnostic and therapeutic approaches have evolved thanks to advances in our understanding of disease mechanisms, which have translated into the recognition of distinct molecular pathways serving as therapeutic targets (Ding et al. 2023).

The understanding of signaling mechanisms has been paralleled by an appreciation of the causative relationship between reversible disease activity and irreversible organ damage in rheumatoid arthritis (RA), where the innovative concept of preventing new joint erosions (and consequent deformities leading to disability) has been introduced as the ultimate treatment goal, termed “disease modification” (Padjen et al. 2020). The treat-to-target principle, which involves attaining low disease activity (or even remission) to achieve disease modification, has become the mainstay of the therapeutic approach in RA and is being gradually applied to other rheumatic diseases (Smolen et al. 2010; Parra Sánchez et al. 2022). Hence, favorable outcomes in inflammatory arthritis have been achieved not only by innovative drugs targeting distinct molecular pathways but also by optimizing therapeutic strategies that do not necessarily rely on a specific drug class (Markusse et al. 2016; Padjen et al. 2020).

Future treatment innovations must still address the gap between therapeutic needs and current possibilities, given that only two-thirds of biologic-naïve RA patients achieve an ACR60 response (equivalent to a 60 percent decline in disease activity) to the first biological drug, as demonstrated in a recent meta-analysis (Mokbel et al. 2023). The likelihood of achieving the desired outcome declines steeply after several treatment attempts in patients who respond inadequately to prior biologics, leaving a residual proportion of patients refractory to treatment (Costa et al. 2017). This is due, at least in part, to our inability to adequately predict the optimal candidate for each drug class. The choice of biologic (or targeted synthetic) drugs in inflammatory arthritis is still influenced as much by comorbidities as by the disease itself (Coates and Gossec 2023). Furthermore, patients with so-called “difficult-to-treat” diseases may have additional confounding factors, such as fibromyalgia, requiring a complex and multimodal therapeutic approach even after the inflammatory component has been well controlled (Nagy et al. 2021; Hofman et al. 2025).

Biomarkers have long been proposed as promising tools to aid clinicians in making optimal diagnostic and therapeutic decisions. Although rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) have been identified as markers of worse prognosis in RA, longitudinal assessment of their serum levels is not recommended during patient follow-up (Aggarwal et al. 2009). Another example is lupus nephritis, where the level of proteinuria has been shown to be an imprecise measure of disease activity, often making it difficult to distinguish between active nephritis, organ damage, and other non-lupus causes of proteinuria (Weeding et al. 2022). A promising novel biomarker with properties superior to proteinuria – and with a strong correlation between urine levels and histologic disease activity – may be urinary interleukin-16. Its superiority may lead to its implementation in routine follow-up of lupus nephritis patients in the coming years (Fava et al. 2022; Häyry et al. 2022).

Several examples have demonstrated that novel therapies developed in hematology have also found application in autoimmune rheumatic diseases. The use of CAR-T cells in patients with severe systemic lupus erythematosus (SLE) has shown promising results, with the ability to “reset” the B cell repertoire while also providing a “backward” translational insight into disease biology (Müller et al. 2024; Wilhelm et al. 2024). Inhibition of the B cell response followed by CAR-T cell infusion has been shown to suppress expression of interferon-alpha-induced genes, suggesting that B cells may play a primary pathogenic role, preceding interferon expression in innate immune cells (Wilhelm et al. 2024). Despite the growing interest in and relevance of the interferon gene signature and its profiling in SLE and related disorders, its integration into routine clinical practice will depend on standardizing quantification methods, which are still lacking (Burska et al. 2023).

On the other hand, the efficacy of B cell inhibition has now been formally demonstrated in a randomized controlled trial of obinutuzumab – a humanized type II anti-CD20 monoclonal antibody already used in hematological malignancies – for patients with active lupus nephritis (Furie et al. 2025). This reinforces the role of anti-CD20 therapy in SLE and lupus nephritis, despite previous negative results in randomized trials of rituximab in these indications (Duxbury et al. 2013).

Despite our increasing ability to understand and phenotype complex rheumatic diseases based on clinical and serological features, our ability to classify them precisely by histological characteristics remains limited. A clear example is the relative nonspecificity of interstitial lung disease (ILD) patterns across rheumatic conditions, where nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) represent the majority of cases across the spectrum of RA and connective tissue diseases (Gutsche et al. 2012). Interestingly, the MUC5B promoter variant rs35705950 has been identified as a shared genetic marker between RA-associated UIP and idiopathic pulmonary fibrosis, suggesting similarities between the two conditions with potential implications for anti-fibrotic treatment strategies in RA-associated ILD (Juge et al. 2018; Liang et al. 2022). In the future, such phenotypic and molecular overlaps may contribute to redefining boundaries between clinical entities.

A persistent challenge is that rheumatic diseases are multidimensional, and no single molecular or radiographic marker – such as HbA1c in diabetes mellitus – can adequately diagnose, monitor, and predict disease progression. Rheumatologists often face diagnostic uncertainty, as clinical judgment remains the gold standard, given that most existing disease criteria sets are intended for classification rather than diagnosis (June and Aggarwal 2014). One exception is the SLE Risk Probability Index (SLERPI), which was developed as a tool to predict the likelihood of SLE in the early diagnostic stage. This tool may improve diagnostic accuracy, particularly in healthcare settings without rheumatology services, and support less experienced clinicians in initiating early diagnosis and treatment (Adamichou et al. 2021).

To conclude, scientific innovations over recent decades have enabled earlier diagnosis and treatment, as well as a deeper understanding of inflammatory rheumatic diseases. Nevertheless, future advances should aim to close the gaps in timely disease recognition, identify the optimal time to initiate treatment, and guide appropriate therapeutic selection.

The correlation between infections and autoimmune diseases has been studied for decades (Mahroum et al. 2024c). Throughout history, this association has gone through various turning points. Acute rheumatic fever (ARF) serves as a key example, illustrating important aspects of this relationship. ARF represents an autoimmune, late sequela of an acute infection caused by group A streptococcus (GAS). The disease is characterized by a multisystemic constellation of symptoms and findings, including musculoskeletal, cardiac, nervous, and cutaneous involvement (Karthikeyan and Guilherme 2018). If analyzed, ARF highlights the following points:

• An infectious agent triggers an autoimmune cascade (molecular mimicry with the production of autoantibodies).
• The autoimmune phenomena result in an autoimmune disease (ARF).
• A time period of 2–6 weeks occurs between infection and the appearance of ARF-related symptoms.
• A disease involves multiple organ systems.
• Once diagnosed, ARF requires a prolonged period of treatment.
• Early detection of infection and proper treatment are key factors in preventing ARF.

Therefore, the critical role of translational medicine in applying the molecular basis of diseases to clinical use – alongside the need for continuous advances in diagnosis and treatment – cannot be overemphasized. ARF is only one example; many autoimmune phenomena and diseases are now known to be directly or indirectly correlated with infections (Mahroum et al. 2024a). Taking the above into account, the bridging process and its clinical implications can be summarized by the following aspects:

1. Triggering effect – A key question in the pathogenesis of diseases in general – and autoimmune or rheumatic diseases in particular – is the identification of the initiating factor.

Accumulated data, including our previous studies, have pointed toward infections as potent stimulators of autoimmune diseases (Mahroum et al. 2023; Mahroum et al. 2024b, c). From a translational medicine perspective, early detection of triggering factors – such as infections in this case – aids in prevention, early diagnosis, and the halting of complications in autoimmune diseases (Buckner 2023). The same principle applies to screening for autoimmune and rheumatic diseases in families with a high predisposition to such disorders (Fig. 1).

Figure 1. 

The association of autoimmunity with SARS-CoV-2 infection. While the number of persons infected with the virus is large, the number of individuals who develop autoimmune manifestations is smaller and appears to be limited to genetically predisposed individuals. These manifestations vary and include Guillain–Barré syndrome, autoimmune thyroid disease, glomerular kidney disease, and immune thrombocytopenic purpura, among others. (Adapted from: Editorial – SARS-CoV-2 – “The Autoimmune Virus Is Still Striking” by Naim Mahroum and Yehuda Shoenfeld, J. Mosaic Autoimmun. 2024).

1. Flare relationship – The triggering effect discussed earlier continues even after autoimmune diseases have already been established. For instance, infections are among the most common causes of exacerbations in autoimmune diseases like systemic lupus erythematosus (SLE) (Zandman-Goddard and Shoenfeld 2005). In fact, the immunological responses and cascades observed in SLE form the basis for understanding this disease, as well as other autoimmune conditions. Therefore, there is an urgent need to understand these processes at the molecular level and translate that knowledge into clinical practice. The latter is the cornerstone of translational medicine and has been previously addressed in detail by numerous studies (Choi and Costenbader 2022).
2. Vaccine-induced phenomena – Vaccines have played a critical role in preventing the spread of highly contagious and fatal diseases. Nevertheless, due to their stimulatory effect on the immune system to produce antibodies against infectious agents, vaccine-induced hyperstimulation of the immune system could induce autoimmune phenomena. Such instances were reported soon after the introduction of COVID-19 vaccines (Mahroum et al. 2022) and were later reiterated in our work at a larger scale (Primorac Padjen et al. 2024). The molecular basis of this effect requires thorough investigation and deeper understanding to enable the development of safer vaccines – crucial tools in the fight against infections. People with a high predisposition to autoimmune diseases are ideal candidates for translational medicine to inform vaccination strategies, enabling protection against infection while also predicting and preventing autoimmune complications.

This editorial focuses on research contributions that highlight the critical interaction between scientific discoveries and clinical applications, as well as on the pressing challenges that remain. By exploring immune mechanisms, advancing diagnostics, and innovating therapeutic strategies, the studies aim to deliver more precise, personalized, and durable healthcare – bridging gaps between disciplines and preparing us for emerging medical challenges.

Conflict of interest

The authors have declared that no competing interests exist.

Ethical statements

The authors declared that no clinical trials were used in the present study.

The authors declared that no experiments on humans or human tissues were performed for the present study.

The authors declared that no informed consent was obtained from the humans, donors or donors’ representatives participating in the study.

The authors declared that no experiments on animals were performed for the present study.

The authors declared that no commercially available immortalised human and animal cell lines were used in the present study.

Use of AI

No use of AI was reported.

Funding

This study is financed by the European Union–NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project No. BG-RRP-2.004-0008.

Author contributions

NM and IV wrote the first draft, GM and TV reviewed and edited the manuscript. All authors were involved in the conceptualization and approved the final version before submission.

Author ORCIDs

Naim Mahroum https://orcid.org/0000-0002-7919-1326

Tsvetelina Velikova https://orcid.org/0000-0002-0593-1272

Georgi Momekov https://orcid.org/0000-0003-2841-7089

Ivan Padjen https://orcid.org/0000-0002-9249-9325

Data availability

All of the data that support the findings of this study are available in the main text.