Adaptive Immune System Research Articles

Endocrine and molecular regulation of seasonal avian immune function.

Birds have evolved seasonal adaptations in multiple aspects of the innate and adaptive immune systems. Seasonal immunological adaptations are crucial for survival in harsh environmental conditions and in response to increased prevalence of acute and chronic diseases. Similar to other vertebrates, birds exhibit remarkable plasticity in cytokine production, chemotaxis, phagocytosis and inflammation across the year. In this review, we provide a comparative perspective on seasonal rhythms in bird immune function. We describe advances in our understanding of annual changes in immune cells and responses to innate and adaptive immune challenges. Then, the role of glucocorticoids, sex steroids, thyroid hormones (THs) and melatonin to act as immunomodulators is described. We then discuss the impact of a major and emerging disease, the high pathogenicity avian influenza, as one of the most critical seasonal diseases with significant implications for poultry and wild bird populations. The review identifies the need to enhance our knowledge of annual rhythms in immune cells and tissues in birds, at molecular, cellular and hormonal levels across the year. Moreover, there is a significant absence of information on sex-specific seasonal variation in immune function. Understanding seasonal immune system dynamics will aid in addressing the negative impacts of pathogenic diseases, minimize global economic losses and aid conservation efforts.This article is part of the Theo Murphy meeting issue 'Circadian rhythms in infection and immunity'.

Novel adaptive immune systems in pristine Antarctic soils

Antarctic environments are dominated by microorganisms, which are vulnerable to viral infection. Although several studies have investigated the phylogenetic repertoire of bacteria and viruses in these poly-extreme environments with freezing temperatures, high ultra violet irradiation levels, low moisture availability and hyper-oligotrophy, the evolutionary mechanisms governing microbial immunity remain poorly understood. Using genome-resolved metagenomics, we test the hypothesis that Antarctic poly-extreme high-latitude microbiomes harbour diverse adaptive immune systems. Our analysis reveals the prevalence of prophages in bacterial genomes (Bacteroidota and Verrucomicrobiota), suggesting the significance of lysogenic infection strategies in Antarctic soils. Furthermore, we demonstrate the presence of diverse CRISPR-Cas arrays, including Class 1 arrays (Types I-B, I-C, and I-E), alongside systems exhibiting novel gene architecture among their effector cas genes. Notably, a Class 2 system featuring type V variants lacks CRISPR arrays, encodes Cas1 and Cas2 adaptation module genes. Phylogenetic analysis of Cas12 effector proteins hints at divergent evolutionary histories compared to classified type V effectors and indicates that TnpB is likely the ancestor of Cas12 nucleases. Our findings suggest substantial novelty in Antarctic cas sequences, likely driven by strong selective pressures. These results underscore the role of viral infection as a key evolutionary driver shaping polar microbiomes.

Metabolic syndrome and its effect on immune cells in apical periodontitis- a narrative review.

Apical periodontitis (AP) is an inflammatory immune response in periapical tissues caused by microbial infections. Failure of root canal treatment or delayed healing is often due to intracanal or extra-radicular bacteria. However, beyond microbial factors, the patient's systemic health can significantly influence the progression and healing of AP. Metabolic syndrome is a risk factor and it is characterized by a cluster of interconnected metabolic risk factors, including abdominal obesity, hyperlipidemia, hypertension, and hyperglycemia. A comprehensive literature review was conducted on apical periodontitis and metabolic syndrome, and their impact on the roles of different immune cell populations. Both AP and metabolic syndrome are inflammatory diseases that involve complex and interwoven immune responses. The affected immune cells are categorized into the innate (neutrophils, macrophages, and dendritic cells) and adaptive immune systems (T cells and B cells). Metabolic diseases and AP are closely correlated, possibly intertwined in a two-way relationship driven by a shared dysregulated immune response. Understanding the pathophysiology and immune mechanisms underlying the two-way relationship between metabolic syndrome and AP can help improve treatment outcomes and enhance the overall well-being of patients with endodontic disease complicated by metabolic syndrome.

Pediatric blepharokeratoconjunctivitis: A challenging ocular surface disease.

Pediatric blepharokeratoconjunctivitis (PBKC) is a chronic and recurrent ocular surface inflammatory disorder affecting children in early life. It is frequently under- or late- diagnosed, representing a potential cause of severe visual morbidity worldwide. An expert panel consensus recently agreed on its definition and proposed diagnostic criteria for suspected and definitive PBKC to reduce confusion and avoid varied terminology previously used in the literature, improving early and precise diagnosis. Previous evidence has pointed to the role of the adaptive immune system in recognizing and handling antigenic eyelid bacterial products, particularly from the cell wall, and the direct toxic and inflammatory effects of their cytolytic exotoxins on the ocular surface. PBKC is a frequent referral in pediatric and cornea clinics characterized by a history of recurrent chalazia, blepharitis, meibomian gland dysfunction, conjunctival hyperemia, phlyctenules formation, and corneal infiltrates with vascularization and scarring. The latter is a major cause of significant visual loss and amblyopia. Current treatment strategies aim to control inflammation on the ocular surface, halt disease progression, and avoid corneal involvement. Further research on pathogenic mechanisms will shed light on novel potential therapeutic strategies. Awareness of PBKC should enhance early diagnosis, prompt adequate treatment, and improve outcomes. We compile current evidence on epidemiology, pathophysiology, clinical spectrum of disease, diagnostic criteria, and management strategies for PBKC.

Elucidating the Role of the T Cell Receptor Repertoire in Myelodysplastic Neoplasms and Acute Myeloid Leukemia.

T cells, as integral components of the adaptive immune system, recognize diverse antigens through unique T cell receptors (TCRs). To achieve this, during T cell maturation, the thymus generates a wide repertoire of TCRs. This is essential for understanding cancer evolution, progression, and the efficacy of immunotherapies. Myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) are hematological neoplasms that are characterized by immune evasion mechanisms, with immunotherapy giving only modest results thus far. Our review of TCR repertoire dynamics in these diseases reveals distinct patterns: MDS patients show increased TCR clonality with disease progression, while AML exhibits varied TCR signatures depending on disease stage and treatment response. Understanding these patterns has important clinical implications, as TCR repertoire metrics may serve as potential biomarkers for disease progression and treatment response, particularly in the context of immunotherapy and stem cell transplantation. These insights could guide patient stratification and treatment selection, ultimately improving therapeutic outcomes in MDS and AML.

T cells in cardiac health and disease.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, with inflammation playing a pivotal role in its pathogenesis. T lymphocytes are crucial components of the adaptive immune system that have emerged as key mediators in both cardiac health and the development and progression of CVD. This Review explores the diverse roles of T cell subsets, including Th1, Th17, γδ T cells, and Tregs, in myocardial inflammatory processes such as autoimmune myocarditis and myocardial infarction. We discuss the contribution of T cells to myocardial injury and remodeling, with emphasis on specific immune receptors, e.g., CD69, that have a critical role in regulating immune tolerance and maintaining the balance between T cell subsets in the heart. Additionally, we offer a perspective on recent advances in T cell-targeted therapies and their potential to modulate immune responses and improve clinical outcomes in patients with CVD and in heart transplant recipients. Understanding the intricate interplay between T cells and cardiovascular pathology is essential for developing novel immunotherapeutic strategies against CVD.

Conditional requirement for dimerization of the membrane-binding module for BTK signaling in lymphocyte cell lines.

Bruton's tyrosine kinase (BTK) is a major drug target in immune cells. The membrane-binding pleckstrin homology and tec homology (PH-TH) domains of BTK are required for signaling. Dimerization of the PH-TH module strongly stimulates the kinase activity of BTK in vitro. Here, we investigated whether BTK dimerizes in cells using the PH-TH module and whether this dimerization is necessary for signaling. To address this question, we developed high-throughput mutagenesis assays for BTK function in Ramos B cells and Jurkat T cells. We measured the fitness costs for thousands of point mutations in the PH-TH module and kinase domain to assess whether dimerization of the PH-TH module and BTK kinase activity were necessary for function. In Ramos cells, we found that neither PH-TH dimerization nor kinase activity was required for BTK signaling. Instead, in Ramos cells, BTK signaling was enhanced by PH-TH module mutations that increased membrane adsorption, even at the cost of reduced PH-TH dimerization. In contrast, in Jurkat cells, we found that BTK signaling depended on both PH-TH dimerization and kinase activity. Evolutionary analysis indicated that BTK proteins in organisms that evolved before the divergence of ray-finned fishes lacked PH-TH dimerization but had active kinase domains, similar to other Tec family kinases. Thus, PH-TH dimerization is a distinct feature of BTK that evolved to exert stricter regulatory control on kinase activity as adaptive immune systems gained increased complexity.

Impacts of donor age and HLA mismatch on HCT outcomes differ according to the donor CMV serostatus in unrelated allo-HCT.

In unrelated allogeneic hematopoietic cell transplantation (allo-HCT), older and/or HLA-mismatched donors are known risk factors for survival outcomes. In healthy individuals, cytomegalovirus (CMV) seropositivity is associated with impaired adaptive immune systems. We assessed whether the adverse effects of donor risk factors are influenced by the donor CMV serostatus. We analyzed 5836 CMV seropositive patients who received unrelated allo-HCT. We divided the entire cohort into two cohorts according to the donor CMV serostatus: CMV-positive (DP) and -negative (DN). We also stratified each cohort into four groups based on donor age (≥ 40 or < 40) and HLA parity (8/8 or 7/8): Young88, Old88, Young78, and Old78. In the CMV-DP cohort, the Old88 (HR 1.20, P = 0.012), Young78 (HR 1.35, P < 0.001), and Old78 (HR 1.60, P < 0.001) groups were associated with inferior OS compared with the Young88 group. On the other hand, in the CMV-DN cohort, neither donor age nor HLA disparity was associated with inferior OS. The adverse impact of donor age was different between the cohorts (CMV-DP; HR 1.19, P = 0.001, CMV-DN; HR 1.04, P = 0.53; P for interaction 0.070), as was the impact of HLA (CMV-DP; HR 1.34, P < 0.001, CMV-DN; HR 1.08 P = 0.23; P for interaction 0.012). The impacts of donor age and HLA mismatch on OS might differ according to the donor CMV serostatus. In unrelated allo-HCT from a CMV seronegative donor, an HLA-mismatched older donor may be able to be selected without affecting OS.

Anti-Human Leukocyte Antigen Antibody Detection from Terasaki's Humoral Theory to Delisting Strategies in 2024.

The human leukocyte antigen (HLA) system plays a critical role in transplant immunology, influencing outcomes through various immune-mediated rejection mechanisms. Hyperacute rejection is driven by preformed donor-specific antibodies (DSAs) targeting HLAs, leading to complement activation and graft loss within hours to days. Acute rejection typically occurs within six months post-transplantation, involving cellular and humoral responses, including the formation of de novo DSAs. Chronic rejection, a key factor in long-term graft failure, often involves class II DSAs and complex interactions between the innate and adaptive immune systems. Advancements in HLA antibody detection, particularly single antigen bead (SAB) assays, have improved the sensitivity and characterization of DSAs. However, these assays face challenges like false positives from denatured antigens and false negatives due to low antibody titers or complement competition. Furthermore, molecular mismatch (MM) analysis has emerged as a potential tool for refining donor-recipient compatibility but faces some issues such as a lack of standardization. Highly sensitized patients with calculated panel-reactive antibodies (cPRA) of 100% face barriers to transplantation. Strategies like serum dilution, novel therapies (e.g., Imlifidase), and delisting approaches could refine immunological risk assessment and delisting strategies are essential to expand transplant opportunities for these patients.

Vertebrate TNF Superfamily: Evolution and Functional Insights.

This study characterizes the evolution of the tumor necrosis factor superfamily (TNFSF) across vertebrate lineages, both cyclostomes and gnathostomes, by combining sequence similarity and synteny data for the genes from 23 model species. The available evidence supports a simple model in which most of the diversity found in living species can be attributed to the expansion of four genes found in an ancestor of all vertebrates before the first of the genome duplications that occurred in the vertebrate lineages. It is inferred that the ancestor of all cyclostomes possessed only six TNFSF genes. A cyclostome-specific genome triplication had little effect on the total number of these genes. The ancestor of all gnathostomes, due to the effect of a second genome duplication plus additional single-gene duplications, already had 21 TNFSF genes. In several gnathostome lineages, particularly in some tetrapods, the TNF superfamily has significantly contracted due to numerous gene losses. This evolutionary model provides a framework for exploring functional data, showing that the descendants of different ancestral genes have acquired distinct roles, most prominently in the innate and adaptive immune systems, which led to a species-specific refinement of which TNFSF genes were conserved or lost. Several data hitherto difficult to interpret (the interactions of very different TNFSF ligands with the same receptors; the ability of the same ligands to bind alternative receptors, with or without death domains; and the cooperation of different ligands in specific functions) can be explained as consequences of the evolutionary history of the TNF superfamily.

Amphibian-Derived Antimicrobial Peptides: Essential Components of Innate Immunity and Potential Leads for New Antibiotic Development.

Like other vertebrates, amphibians possess innate and adaptive immune systems. At the center of the adaptive immune system is the Major Histocompatibility Complex. The important molecules of innate immunity are antimicrobial peptides (AMPs). These peptides are secreted by granular glands in the skin and protect the animal against microorganisms entering its body through the skin. AMPs offer an effective and rapid defense against pathogenic microorganisms and have cationic and amphiphilic structures. These peptides are small gene-encoded molecules of 8-50 amino acid residues synthesized by ribosomes. These small molecules typically exhibit activity against bacteria, viruses, fungi, and even cancer cells. It is known that today's amphibian AMPs originated from a common precursor gene 150 million years ago and that the origin of these peptides is preprodermaseptins. Today, antibiotic resistance has occurred due to the incorrect use of antibiotics. Traditional antibiotics are becoming increasingly inadequate. AMPs are considered promising candidates for the development of new-generation antibiotics. Therefore, new antibiotic discoveries are needed. AMPs are suitable molecules for new-generation antibiotics that are both fast and have different killing mechanisms. One of the biggest problems in the clinical applications of AMPs is their poor stability. AMPs generally have limited tropical applications because they are sensitive to protease degradation. Coating these peptides with nanomaterials to make them more stable can solve this problem.

Lipid Antigens: Revealing the Hidden Players in Adaptive Immune Responses.

Traditionally, research on the adaptive immune system has focused on protein antigens, but emerging evidence has underscored the essential role of lipid antigens in immune modulation. Lipid antigens are presented by CD1 molecules and activate invariant natural killer T (iNKT) cells and group 1 CD1-restricted T cells, whereby they impact immune responses to pathogens and tumors. Recent advances in mass spectrometry, imaging techniques, and lipidomics have revolutionized the identification and characterization of lipid antigens and enhanced our understanding of their structural diversity and functional significance. These advancements have paved the way for lipid-based vaccines and immunotherapies through the application of nanoparticles and synthetic lipid antigens designed to boost immune responses against cancers and infectious diseases. Lipid trafficking, CD1 molecule interactions, and the immune system's response to lipid antigens are yet to be completely understood, particularly in the context of autoimmunity and microbial infections. In the years to come, continued research efforts are needed to uncover its underlying biological mechanisms and to exploit the full potential of therapies directed against lipid antigens.

Incipient and subclinical tuberculosis: a narrative review.

Mycobacterium tuberculosis has been known to infect humans for eons. It is an airborne infectious disease transmitted through droplet nuclei of 1 to 5 µm in diameter. Historically, tuberculosis (TB) was considered a distinct condition characterized by TB infection and active TB disease. However, recently, the concept of a dynamic spectrum of infection has emerged, wherein the pathogen is initially eradicated by the innate or adaptive immune system, either in conjunction with or independently of T cell priming. Other categories within this spectrum include TB infection, incipient TB, subclinical TB, and active TB disease. Various host- and pathogen-related factors influence these categories. Furthermore, subclinical TB can facilitate the spread of infection within the community. Due to its asymptomatic nature, there is a risk of delayed diagnosis, and some patients may remain undiagnosed. Individuals with subclinical TB may stay in this stage for an indeterminate period without progressing to active TB disease, and some may even experience regression. Early diagnosis and treatment of TB are essential to meet the 2035 targets outlined in the end-TB strategy. This strategy should also include incipient and subclinical TB. This review will focus on the definition, natural history, burden, trajectory, transmissibility, detection, and management of early-stage TB.

RNA sensing at the crossroads of autoimmunity and autoinflammation.

Immune-mediated diseases are common in humans. The immune system is a complex host defense system that evolved to protect us from pathogens, but also plays an important role in homeostatic processes, removing dead or senescent cells, and participating in tumor surveillance. The human immune system has two arms: the older innate immune system, and the newer adaptive immune system. Sensing of foreign RNA is critical to the innate immune system's ability to recognize pathogens, especially viral infections. However, RNA sensors are also strongly implicated in autoimmune and autoinflammatory diseases, highlighting the importance of balancing pathogen recognition with tolerance to host RNAs that can resemble their viral counterparts. We describe how RNA sensors bind their ligands, how this binding is coupled to upregulation of Type I interferon-stimulated genes, and the ways in which mutations in RNA sensors and genes that play important roles in RNA homeostasis have been linked to autoimmune and autoinflammatory diseases.

Chlamydia trachomatis impairs T cell priming by inducing dendritic cell death.

The lack of effective adaptive immunity against Chlamydia trachomatis leads to chronic or repeated infection and serious disease sequelae. Dendritic cells (DCs) are professional antigen-presenting cells that are crucial for the activation of T cells during C. trachomatis infection. cDC1s and cDC2s are the two main DC subsets responsible for T cell priming, but little is known about how C. trachomatis affects their ability to prime T cells. Using a mouse model of infection, we found that C. trachomatis uptake reduced the viability of cDC1s and cDC2s both in vitro and in vivo, with cDC1s experiencing more death. DC death was mainly due to apoptosis and is alleviated in Casp3/7 or Bak1/Bax knockout DCs. In addition, we observed that C. trachomatis-specific CD8+ T cells were preferentially activated by cDC1s. Reduction in DC viability by C. trachomatis impaired the ability of infected DCs to activate T cells upon co-culture, although in the case of CD8+ T cell priming, controlling for viability was insufficient to fully rescue the defect. RNA sequencing of DCs from infected mice showed upregulation of cell death pathways, supporting our observations of DC death caused by C. trachomatis. Finally, we validated our findings with human DCs in vitro, observing C. trachomatis-induced cell death. These results indicate that C. trachomatis may evade the adaptive immune system by directly inducing cell death in DCs.

Abnormal T-Cell Activation And Cytotoxic T-Cell Frequency Discriminates Symptom Severity In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating but poorly-understood disease. ME/CFS symptoms can range from mild to severe, and include immune system effects alongside incapacitating fatigue and post-exertional disease exacerbation. In this study, we examined immunological profiles of people living with ME/CFS by flow cytometry, focusing on cytotoxic cells, to determine whether people with mild/moderate (n= 43) or severe ME/CFS (n=53) expressed different immunological markers. We found that people with mild/moderate ME/CFS had increased expression of cytotoxic effector molecules alongside enhanced proportions of early-immunosenescence cells, determined by the CD28 - CD57 - phenotype, indicative of persistent viral infection. In contrast, people with severe ME/CFS had higher proportions of activated circulating lymphocytes, determined by CD69 + and CD38 + expression, and expressed more pro-inflammatory cytokines, including IFNγ, TNF and IL-17, following stimulation in vitro , indicative of prolonged non-specific inflammation. These changes were consistent across different cell types including CD8 + T cells, mucosal associated invariant T cells and Natural Killer cells, indicating generalised altered cytotoxic responses across the innate and adaptive immune system. These immunological differences likely reflect different disease pathogenesis mechanisms occurring in the two clinical groups, opening up opportunities for the development of prognostic markers and stratified treatments.

The primary mechanisms underlying atopic dermatitis.

Atopic dermatitis (AD) is a complex skin disease frequently linked with other atopic symptoms such allergic rhinitis and asthma. The disease's history consists of persistent relapses with extreme pruritus, which lowers quality of life. AD has become a global health concern as its incidence has increased over the last few decades. It ranks as the third most common dermatologic disorder. There are several open questions about the mechanisms underlying atopic dermatitis (AD), This review aims to emphasize the recent advances in scientific research regarding the pathophysiologic mechanism of AD and the clinical application of these factors. A PubMed search was performed using the keywords "Atopic Dermatitis (AD)", "epidemiology", "clinical presentation", "diagnosis", "pathophysiology", "genetic defect", "impaired skin barrier", "immune dysregulation". The search strategy included meta-analyses, clinical trial, observational studies, and reviews. Atopic dermatitis affects over 2 million children worldwide, with a lifetime incidence of up to 20%. New data suggest that its incidence is still growing, particularly in low-income nations. AD is diagnosed clinically using the patient's medical history, particular clinical symptoms, and the elimination of other non-inflammatory skin conditions. The pathogenesis of AD is extremely complicated and involves several etiologies, including genetics, the microbiome, abnormalities in the skin barrier, along with dysfunctional innate and adaptive immune systems. Recent research has improved our understanding of disease pathophysiology in atopic dermatitis. Current and future clinical trials are expected to continue clarifying this complex and heterogeneous skin disease, and to develop medications that promise more effective therapy, particularly for individuals with limited response to conventional treatments.

Estrogen, estrogen receptor and the tumor microenvironment of NSCLC

AbstractLung cancer remains the foremost cause of cancer‐related mortality worldwide. Clinical observations reveal a notable increase in both the proportion and mortality rate among female non‐small cell lung cancer (NSCLC) patients compared to males, a trend that continues to escalate. Extensive preclinical research underscores the pivotal role of estrogen in the initiation, progression, prognosis, and treatment response of NSCLC. Estrogen receptors are widely expressed in stromal and immune cells, influencing cellular activities across innate and adaptive immune systems. Immune evasion mechanisms significantly impact tumor development and outcomes, with immunotherapy offering promise in NSCLC by targeting these mechanisms. The intriguing gender disparities in immunotherapy responses prompt an exploration into the data on NSCLC occurrence, progression, and gender‐specific immunotherapy. Evidence highlights estrogen's contribution to a tumor‐permissive microenvironment, influencing various cells including cancer‐associated fibroblasts, macrophages, neutrophils, dendritic cells, natural killer cells, B cells, and T cells. Gender‐specific variations in NSCLC occurrence, development, prognosis, and treatment efficacy likely stem from interactions between estrogen, lung cancer cells, and these estrogen‐responsive cells, shaping a microenvironment conducive to tumor progression. Clarifying estrogen's role and its signaling pathways in NSCLC may unveil novel therapeutic strategies to modify the tumor microenvironment or enhance immunotherapy efficacy.

CRISPR/Cas Systems as Diagnostic and Potential Therapeutic Tools for Enterohemorrhagic Escherichia coli.

Following its discovery as an adaptive immune system in prokaryotes, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system has been developed into a multifaceted genome editing tool. This review compiles findings aimed at implementation of this technology for selective elimination or attenuation of enterohemorrhagic Escherichia coli (EHEC). EHEC are important zoonotic foodborne pathogens that cause hemorrhagic colitis and can progress to the life-threatening hemolytic uremic syndrome (HUS). Advancements in the application of CRISPR methodology include laboratory detection and identification of EHEC, genotyping, screening for pathogenic potential, and engineering probiotics to reduce microbial shedding by cattle, the primary source of human infection. Genetically engineered phages or conjugative plasmids have been designed to target and inactivate genes whose products are critical for EHEC virulence.

Adaptive ımmune system evaluation in familial mediterranean fever: clinical and ımmunological analysis.

Familial Mediterranean Fever is a common genetic autoinflammatory disease prevalent in the Mediterranean region. The clinical course of the disease is characterized by fever and serositis attacks. While defects in the innate immune system are known to play a role in the pathogenesis of the disease, the impact of the adaptive immune system remains unclear. Therefore, the main objective of this study is to analyze the adaptive immune system cells in FMF patients and investigate their relationship with the disease. Our study includes 88 FMF patients with confirmed MEFV gene mutations. The demographic characteristics, clinical symptoms, genetic profiles, treatment methods, and any accompanying diseases of the patients were thoroughly examined. Additionally, lymphocyte subpopulations were analyzed using flow cytometry, and inflammatory markers and immunoglobulin levels were evaluated. Significant differences were observed in the distribution of adaptive immune system cells in FMF patients compared to the healthy reference group. In the analysis of lymphocyte subgroups, levels of CD3, CD4, CD19, CD16+56+, CD3CD4CD45RACD31, CD4+CD45RA+, CD8+CD45RA+, CD19+CD27+IgD+IgM+, CD19+CD27+IgD-IgM-, and CD19+CD38+CD21 were found to be lower compared to healthy individuals. Additionally, CD8, CD19+CD27-IgD+, and CD3/CD8/TCRGD cells were found to be higher. Moreover, in FMF patients with accompanying diseases, CD3, CD4, and CD19 values were statistically lower (p<0.001). This study reveals that adaptive immune system cells are affected in FMF patients, suggesting their significant role in the disease's pathophysiology. Immunological evaluations should be prioritized in the management of FMF, enabling personalized treatment plans for more effective outcomes.