Immune Complex Formation Research Articles

DOENÇA RENAL CRÔNICA CONCOMITANTE À ERLIQUIOSE: RELATO DE CASO

Kidney disease can range from acute kidney injury to chronic kidney disease, often caused by inflammation that impairs filtration. When kidney function is compromised, toxins accumulate, which can lead to kidney failure. In advanced cases, dialysis treatment becomes necessary. Other associated pathologies, such as ehrlichiosis, can make the condition irreversible. Ehrlichiosis triggers an inflammatory response affecting the kidneys, with the formation of immune complexes during infection. These complexes deposit in the renal capillaries, causing glomerulonephritis, an inflammation that impairs the function of the glomeruli, responsible for blood filtration. The purpose of this report is to present a case where kidney disease developed concomitantly with ehrlichiosis. In this case, an animal was referred to a veterinary hospital for dialysis treatment due to kidney disease. Laboratory tests were conducted, including a complete blood count, biochemical analysis, rapid ehrlichiosis test, and PCR, which confirmed the presence of active ehrlichiosis infection. Additionally, hemodialysis and dialysis sessions were performed, among other treatments. This case highlights the complexity and challenges of treating chronic kidney disease aggravated by ehrlichiosis, emphasizing the importance of advanced therapies and the need for ethical planning to balance available resources and the animal's quality of life. Raising awareness among pet owners about the risks, the importance of early diagnosis, correct treatment, and continuous monitoring are fundamental measures that can help in the early detection of kidney impairment and increase the chances of successful treatment.

A BIOSSEGURANÇA NO ÂMBITO DA ODONTOLOGIA: REVISÃO DA LITERATURA

Kidney disease can range from acute kidney injury to chronic kidney disease, often caused by inflammation that impairs filtration. When kidney function is compromised, toxins accumulate, which can lead to kidney failure. In advanced cases, dialysis treatment becomes necessary. Other associated pathologies, such as ehrlichiosis, can make the condition irreversible. Ehrlichiosis triggers an inflammatory response affecting the kidneys, with the formation of immune complexes during infection. These complexes deposit in the renal capillaries, causing glomerulonephritis, an inflammation that impairs the function of the glomeruli, responsible for blood filtration. The purpose of this report is to present a case where kidney disease developed concomitantly with ehrlichiosis. In this case, an animal was referred to a veterinary hospital for dialysis treatment due to kidney disease. Laboratory tests were conducted, including a complete blood count, biochemical analysis, rapid ehrlichiosis test, and PCR, which confirmed the presence of active ehrlichiosis infection. Additionally, hemodialysis and dialysis sessions were performed, among other treatments. This case highlights the complexity and challenges of treating chronic kidney disease aggravated by ehrlichiosis, emphasizing the importance of advanced therapies and the need for ethical planning to balance available resources and the animal's quality of life. Raising awareness among pet owners about the risks, the importance of early diagnosis, correct treatment, and continuous monitoring are fundamental measures that can help in the early detection of kidney impairment and increase the chances of successful treatment.

Hepatocellular carcinoma antibodies preferably identify nitro-oxidative-DNA lesions induced by 4-Chloro-orthophenylenediamine and DEANO.

The widespread use of oxidative hair colouring cosmetics threatens public health. Phenylenediamine derivatives serve as the main pigment in permanent hair colours. They interact with biological macromolecules, altering their functional and structural physiology. The study aimed to investigate the effect of a typical synthetic hair dye pigment, 4-Chloro-orthophenylenediamine (4-Cl-OPD), under a nitrating environment of DEANO on the calf thymus DNA molecule. The results showed single-stranded regions, base/sugar-phosphate backbone alterations, molecular changes, and nitro-oxidative lesions. These modifications are referred to as neo-epitopes on the DNA molecule. IgGs from cancer patients with a history of permanent hair dye use were screened for the recognition of neo-epitopes on DNA molecules. Hepatocellular carcinoma IgG showed the highest binding with 56% inhibition in the competition ELISA. The immune complex formation was observed through electrophoretic mobility shift assay. In conclusion, synthetic hair dye users are likely to present with heightened immunological triggers under elevated nitric oxide levels. The study reports chronic hair dye exposure as one of the factors responsible for altering the intricacies of the DNA's microarchitectural structure and inducing neo-epitopes on the molecule. The physiological status of NO may define the susceptibility towards 4-Cl-OPD and humoral response in hair dye users. Persistent nitro-oxidative stress due to 4-Cl-OPD and NO may induce a heightened immune response against neoepitopes in the nitro-oxidatively modified DNA. Therefore, chronic hair dye exposure may be identified as a risk to human health. These findings may contribute to a better understanding and reinforcement of hair dye as one of the modifiable risk factors responsible for the pro-inflammatory carcinogenic environment.

Exploring the Contrasts and Similarities of Dengue and SARS-CoV-2 Infections During the COVID-19 Era.

Extensive research has been conducted on the SARS-CoV-2 virus in association with various infectious diseases to understand the pathophysiology of the infection and potential co-infections. In tropical countries, exposure to local viruses may alter the course of SARS-CoV-2 infection and coinfection. Notably, only a portion of the antibodies produced against SARS-CoV-2 proteins demonstrate neutralizing properties, and the immune response following natural infection tends to be temporary. In contrast, long-lasting IgG antibodies are common after dengue virus infections. In cases where preexisting antibodies from an initial dengue virus infection bind to a different dengue serotype during a subsequent infection, there is a potential for antibody-dependent enhancement (ADE) and the formation of immune complexes associated with disease severity. Both SARS-CoV-2 and dengue infections can result in immunodeficiency. Viral proteins of both viruses interfere with the host's IFN-I signaling. Additionally, a cytokine storm can occur after viral infection, impairing a proper response, and autoantibodies against a wide array of proteins can appear during convalescence. Most of the reported autoantibodies are typically short-lived. Vaccines against both viruses alter the immune response, affecting the course of viral infection and enhancing clearance. A comprehensive analysis of both viral infections and pathogenicity is revisited to prevent infection, severity, and mortality.

Lessons from IgA Nephropathy Models.

IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide; however, the underlying mechanisms of this disease are not fully understood. This review explores several animal models that provide insights into IgAN pathogenesis, emphasizing the roles of aberrant IgA1 glycosylation and immune complex formation. It discusses spontaneous, immunization, and transgenic models illustrating unique aspects of IgAN development and progression. The animal models, represented by the grouped ddY (gddY) mouse, have provided guidance concerning the multi-hit pathogenesis of IgAN. In this paradigm, genetic and environmental factors, including the dysregulation of the mucosal immune system, lead to increased levels of aberrantly glycosylated IgA, nephritogenic immune complex formation, and subsequent glomerular deposition, followed by mesangial cell activation and injury. Additionally, this review considers the implications of clinical trials targeting molecular pathways influenced by IgAN (e.g., a proliferation-inducing ligand [APRIL]). Collectively, these animal models have expanded the understanding of IgAN pathogenesis while facilitating the development of therapeutic strategies that are currently under clinical investigation. Animal-model-based studies have the potential to facilitate the development of targeted therapies with reduced side effects for IgAN patients.

Amyloid-β (Aβ) immunotherapy induced microhemorrhages are linked to vascular inflammation and cerebrovascular damage in a mouse model of Alzheimer’s disease

BackgroundAnti-amyloid-β (Aβ) immunotherapy trials have revealed amyloid-related imaging abnormalities (ARIA) as the most prevalent and serious adverse events linked to pathological changes in cerebral vasculature. Recent studies underscore the critical involvement of perivascular macrophages and the infiltration of peripheral immune cells in regulating cerebrovascular damage. Specifically, Aβ antibodies engaged at cerebral amyloid angiopathy (CAA) deposits trigger perivascular macrophage activation and the upregulation of genes associated with vascular permeability. Nevertheless, further research is needed to understand the immediate downstream consequences of macrophage activation, potentially exacerbating CAA-related vascular permeability and microhemorrhages linked to Aβ immunotherapy.MethodsThis study investigates immune responses induced by amyloid-targeting antibodies and CAA-induced microhemorrhages using RNA in situ hybridization, histology and digital spatial profiling in an Alzheimer's disease (AD) mouse model of microhemorrhage.ResultsIn the present study, we have demonstrated that bapineuzumab murine surrogate (3D6) induces profound vascular damage, leading to smooth muscle cell loss and blood–brain barrier (BBB) breakdown. In addition, digital spatial profiling (DSP) reveals that distinct immune responses contribute to vascular damage with peripheral immune responses and perivascular macrophage activation linked to smooth muscle cell loss and vascular fibrosis, respectively. Finally, RNA in situ hybridization identifies two distinct subsets of Trem2+ macrophages representing tissue-resident and monocyte-derived macrophages around vascular amyloid deposits. Overall, these findings highlight multifaceted roles of immune activation and vascular damage in driving the development of microhemorrhage.ConclusionsIn summary, our study has established a significant link between CAA-Aβ antibody immune complex formation, immune activation and vascular damage leading to smooth muscle cell loss. However, the full implications of this cascade on the development of microhemorrhages requires further exploration. Additional investigations are warranted to unravel the precise molecular mechanisms leading to microhemorrhage, the interplay of diverse immune populations and the functional roles played by various Trem2+ macrophage populations in response to Aβ immunotherapy.

The Role of Aspergillus Antibody Detection in Allergic Bronchopulmonary Aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung disorder characterized by an exaggerated immune response to fungal allergens, particularly from Aspergillus fumigatus. ABPA leads to excessive mucus production and impaired mucociliary clearance. When A. fumigatus conidia are inhaled, they germinate, release exoproteases and other substances that further impede mucociliary clearance, and activate the immune response. The immune response is known by an exaggerated Th2 response to Aspergillus antigens, leading to production of IgE antibodies, eosinophilic infiltration of the lungs, and the formation of immune complexes. These immune complexes can deposit in the lung tissue, leading to airway inflammation, bronchiectasis, and fibrosis. This disease mainly occurs in individuals diagnosed with bronchial asthma and cystic fibrosis. Increased levels of A. fumigatus total IgE and specific IgE, IgG, and IgA antibodies, play a role in diagnosing patients with ABPA.

HEV ORF2 protein-antibody complex deposits are associated with glomerulonephritis in hepatitis E with reduced immune status

Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN develops in parallel with increasing glomerular deposition of a non-infectious, genome-free and non-glycosylated HEV open reading frame 2 (ORF2) capsid protein. No productive HEV infection of kidney cells is detected. Patients with acute hepatitis E display similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN in the immunocompromised state. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a potential mechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN as a distinct entity and suggest therapeutic implications.

Circulating Immune Complexes and Complement Activation in Sensitized Kidney Transplant Recipients.

Chronic antibody-mediated rejection in kidney transplantation is a common cause of graft loss in the late post-transplant period. In this process, the role of the classical complement activation pathway is crucial due to the formation of immune complexes between donor-specific antibodies (DSAs) and donor antigens and the attachment of the C1q complement fragment. This study aimed to determine the levels of circulating C1q immunocomplexes (CIC-C1q) and complement activation (CH50), in sensitized kidney transplant recipients (KTRs). In this cross-sectional study we used serum samples from KTRs with de novo or preformed DSAs (n = 14), KTRs without DSAs (n = 28), and 22 subjects with no history of chronic kidney disease (controls). C1q immunocomplexes and CH50 concentration in serum were measured with the enzyme immunoassay (EIA) kit MicroVue CIC-C1q (Quidel, Athens, OH, USA) and EIA kit MicroVue CH50 (Quidel, OH, USA), respectively. Higher concentrations of CIC-C1q was observed in KTRs with DSAs in comparison with controls and with KTRs with no DSAs (6.8 ± 2.7 and 4.8 ± 1.9 vs. 5.0 ± 1.2 μg Eq/mL, respectively, p < 0.01). We found no difference in CIC-C1q between KTRs with no DSAs and controls. CIC-C1q levels were positively correlated with DSA titer. CH50 levels were decreased in KTRs with DSAs in comparison with controls and KTRs with no DSAs (39 ± 15 vs. 68 ± 40 and 71 ± 34 U Eq/mL, respectively, p < 0.01). There was no difference in CH50 between DSA-negative KTRs and controls. Kidney transplant recipients with DSAs had increased serum levels of C1q immunocomplexes and increased classical pathway complement activation.

JAK inhibitors in systemic lupus erythematosus: Translating pathogenesis into therapy.

Systemic lupus erythematosus (SLE) is a complex multi-organ autoimmune disease marked by the production of autoantibodies against nuclear structures, formation of immune complexes, and chronic inflammation triggered by their tissular deposition. SLE is characterized by alternating periods of relapse and remission and each flare has the potential to cause new organ damage related to either the disease process or the medication toxicity. Despite remarkable progress across its multiple domains, SLE is still an area with many unmet needs, calling for innovative and practical solutions. The efforts of the drug development programme in lupus have led to considerable growth in the last decade, owing to the approval of belimumab, anifrolumab, and voclosporin. The increasing understanding of the pathogenesis of the disease has enabled the exploration of novel therapeutic strategies. New discoveries in the intricate cytokine kaleidoscope of lupus have made the concept of targeted therapy an attractive and promising research focus. JAK inhibitors are oral targeted therapies approved for a wide variety of diseases across the Rheumatology, Gastroenterology, Dermatology, and Haematology fields. Multiple JAKis are currently being investigated in SLE. This paper aims to summarize existing data coming from both clinical trials and case reports regarding the use of JAK inhibitors in SLE.

Persistent Splenic-Derived IgM Preferentially Recognize Factor VIIIA2 and C2 Domain Epitopes but Do Not Alter Antibody Production

The most significant treatment complication for patients with hemophilia A is the development of neutralizing immunoglobin G (IgG), termed inhibitors, against factor VIII (FVIII) which prevent FVIII replacement therapy. Low titers of FVIII-specific immunoglobin M (IgM) have been identified in hemophilia A patients with and without inhibitors, as well as healthy individuals. However, the duration and influence of IgM on the immune response to FVIII remains unclear. To characterize the binding interactions of persistently secreted FVIII-specific IgM in hemophilia A mice and assess their effect on IgG antibody development. Splenic-derived monoclonal antibodies (MAbs) from immunized FVIII knockout mice were isolated and purified using hybridoma technology. Binding interactions were assessed utilizing a novel fluid-phase ELISA and computational modeling with HADDOCK to account for weak IgM binding. Sixteen porcine cross-reactive and non-inhibitory FVIII-specific IgM MAbs were identified. RNA sequencing of FVIII-specific IgM revealed 13 unique VDJ/VJ sequences indicating derivation from 13 unique B cell clones. IgM demonstrated polyclonal and polyreactive binding to FVIII in vitro and in silico. Molecular docking studies with reconstructed IgM VDJ/VJ regions identified frequent IgM interactions with amino acid residues K376, T381, K437, R2215 or K2249 within the FVIII A2 and C2 domains. Injections of individual IgM prior to FVIII exposure and co-injection of FVIII/IgM immune complexes did not affect de novo FVIII antibody production. Persistent FVIII-specific IgM are polyclonal but preferentially bind the A2 and C2 domains and FVIII/IgM immune complex formation do not significantly alter inhibitor development.

Natural variation in maize ZmLecRK1 fine-tunes co-receptor interactions to boost immunity

Pattern recognition receptors (PRRs) are integral to plant immunity, functioning as the first line of defense against pathogens. Among these, receptor kinases (RKs) play a critical role in recognizing external signals and initiating immune responses. Recent studies by Li et al. (2024) have identified the G-type lectin receptor kinase ZmLecRK1 in maize as essential for resistance to Pythium aphanidermatum and other fungal pathogens. A key finding is that a resistant variant of ZmLecRK1, which carries an alanine at position 404, has emerged in maize, while the ancestral form, with a serine at this position, is conserved across most grasses. This amino acid substitution significantly influences the interaction with the co-receptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR KINASE 1 (BAK1), enhancing immune complex formation and subsequent defense signaling. This work underscores the importance of genetic variation in enhancing disease resistance, offering potential strategies for crop improvement through targeted genetic modification.

Mechanisms that potentially contribute to the development of post-streptococcal glomerulonephritis.

Post-streptococcal glomerulonephritis (PSGN) is primarily associated with preceding Group A streptococcal skin or throat infections, now mainly observed in economically disadvantaged communities. This condition significantly predisposes individuals to later-life chronic kidney disease and concurrent renal complications, with the elderly experiencing increased severity and less favourable outcomes. Streptococcal pyrogenic exotoxin B and nephritis associated plasmin receptor are identified nephritogenic antigens (nephritogens). Pathogenesis of PSGN is multifactorial. It can involve the formation of antigen-antibody immune complexes, causing inflammatory damage to renal glomeruli. Deposition of circulating immune complexes or in situ formation of immune complexes in glomeruli, or both, results in glomerulonephritis. Additionally, molecular mimicry is hypothesised as a mechanism, wherein cross-reactivity between anti-streptococcal antibodies and glomerular intrinsic matrix proteins leads to glomerulonephritis. Besides, as observed in clinical studies, streptococcal inhibitor of complement, a streptococcal-secreted protein, can also be associated with PSGN. However, the interplay between these streptococcal antigens in the pathogenesis of PSGN necessitates further investigation. Despite the clinical significance of PSGN, the lack of credible animal models poses challenges in understanding the association between streptococcal antigens and the disease process. This review outlines the postulated mechanisms implicated in the development of PSGN with possible therapeutic approaches.

Autoantibody mediated deficiency of IL-36-receptor antagonist in a subset of patients with psoriasis and psoriatic arthritis

ObjectivePsoriatic arthritis (PsA) is known as a seronegative form of spondylarthropathy. The interleukin-36 cytokine family may have a major role in disease pathogenesis and particularly the related cutaneous manifestations. In light of our recent observations on (transient) autoantibody phenotypes neutralizing endogenous anti-inflammatory receptor antagonists (progranulin, IL-1Ra) in different inflammatory conditions, we set out to investigate the potential role of such antibodies targeting IL-36 cytokine family members in PsA and psoriasis without arthritic manifestations (Pso). MethodsIn the present study we screened for hypothetic autoantibodies against the anti-inflammatory mediators IL-36 receptor antagonist (IL-36Ra) and anti-inflammatory IL-38 in PsA, Pso and inflammatory and healthy controls. Serum samples of patients with PsA (n = 254), Pso (n = 100), systemic lupus erythematosus (SLE, n = 50), rheumatoid arthritis (RA, n = 100), ulcerative colitis (UC, n = 50), Crohn´s disease (CD, n = 50), and healthy controls (n = 237) were screened for autoantibodies against IL-36Ra and IL-38 as well as IL-36Ra levels by ELISA. Biochemical analysis for immune complexes and atypic protein isoforms as well as IL-36 signaling reporter assays were performed. ResultsAnti-IL-36Ra antibodies were detected in five out of 100 (5.0 %) patients with Pso, in 12 of 254 (4.72 %) patients with PsA and in one of 50 (2 %) patients with CD, but in none of the other investigated inflammatory or healthy controls. The IL-36Ra autoantibodies belonged to the IgG1 subclass and their titers ranged between 1:200 to 1:1600. They resulted in immune-complex formation, depletion of serum IL-36Ra levels and were functional in terms of facilitating unrestricted IL-36 signaling. ConclusionIL-36Ra autoantibodies were found in subgroups of patients with Pso and PsA and may drive respective pathology.

Proteomic analysis of laser captured tubular tissues reveals complement activation and mitochondrial dysfunction in autoimmune related kidney diseases

Autoimmune related kidney diseases (ARKDs), including minimal change nephropathy (MCN), membranous nephropathy (MN), IgA nephropathy (IgAN), and lupus nephritis (LN), significantly affect renal function. These diseases are characterized by the formation of local immune complexes and the subsequent activation of the complement system, leading to kidney damage and proteinuria. Despite the known patterns of glomerular injury, the specific molecular mechanisms that contribute to renal tubular damage across ARKDs remain underexplored. Laser capture microdissection and liquid chromatography–tandem mass spectrometry (LC–MS/MS) were used to conduct a comparative proteomic analysis of renal tubular tissues from formalin-fixed paraffin-embedded samples. The cohort comprised of 10 normal controls (NC), 5 MCN, 4 MN, 17 IgAN, and 21 LN patients. Clinical parameters and histopathological assessments were integrated with proteomic findings to comprehensively investigate underlying pathogenic processes. Clinical evaluation indicated significant glomerular damage, as reflected by elevated urinary protein levels and reduced plasma albumin levels in patients with ARKD. Histological analyses confirmed varying degrees of tubular damage and deposition of immune complexes. Proteomic analyses identified significant changes in protein expression, particularly in complement components (C3, C4A, C4B, C8G, CFB, and SERPINA1) and mitochondrial proteins (ATP5F1E and ATP5PD), highlighting the common alterations in the complement system and mitochondrial proteins across ARKDs. These alterations suggest a novel complement–mitochondrial–epithelial–mesenchymal transition (EMT) pathway axis that contributes to tubular damage in ARKDs. Notably, significant alterations in CFB in tubular ARKD patients were revealed, implicating it as a therapeutic target. This study underscores the importance of complement activation and mitochondrial dysfunction in the pathogenesis of ARKDs, and proposes CFB as a potential therapeutic target to inhibit complement activation and mitigate tubular damage. Future research should validate the complement-mitochondrial-EMT pathway axis and explore the effects and mechanisms of CFB inhibitors in alleviating ARKD progression.

Association between systemic lupus erythematosus and common female reproductive system malignancies

Lymphocytes are important for protective immunity against infections and cancers, and dysregulation of the immune system may lead to systemic lupus erythematosus (SLE). Metabolic adaptation regulates the fate of lymphocytes. The immune microenvironment is vital role in both SLE and gynecological malignancies. The disruption of the immune microenvironment in SLE is one of the key factors leading to disease occurrence. Overactive autoimmunity indices the body to attack its own tissues, leading to the formation of immune complexes that further trigger tissue damage and inflammation. This imbalance in the immune microenvironment affects the progression of SLE and may also indirectly affect the occurrence of gynecological cancers. For gynecological cancers, immune cells, cytokines, and chemokines in the tumor microenvironment jointly comprise a complex network, and their interactions determine cancer growth, invasion, and metastasis. Mendelian randomization analysis revealed that SLE does not have a statistically significant causal effect on the risk of common cancers of the female reproductive system such as cervical, endometrial, and ovarian cancers in the European population. However, the odds ratio < 1 in the inverse variance weighted results suggest the potential of SLE as a protective factor for endometrial cancer.

IgA Nephropathy: Significance of IgA1-Containing Immune Complexes in Clinical Settings.

IgA nephropathy (IgAN) is considered to be an autoimmune disease characterized by the formation of IgA1-containing immune complexes in the circulation and glomerular immunodeposits. Extensive research has identified multiple genetic, immunological, and environmental factors contributing to disease development and progression. The pathogenesis of IgAN is considered a multifactorial process involving the formation of immune complexes wherein aberrantly O-glycosylated IgA1 is recognized as an autoantigen. Consequently, the clinical presentation of IgAN is highly variable, with a wide spectrum of manifestations ranging from isolated microscopic hematuria or episodic macroscopic hematuria to nephrotic-range proteinuria. Whereas some patients may exhibit a slowly progressive form of IgAN, others may present with a rapidly progressive glomerulonephritis leading to kidney failure. Development of the treatment for IgAN requires an understanding of the characteristics of the pathogenic IgA1-containing immune complexes that enter the glomerular mesangium and induce kidney injury. However, not all details of the mechanisms involved in the production of galactose-deficient IgA1 and immune-complex formation are fully understood. Here, we review what we have learned about the characteristics of nephritogenic IgA1 in the half-century since the first description of IgAN in 1968.

Interplay between Comorbidities and Long COVID: Challenges and Multidisciplinary Approaches.

Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.

Cell Free DNA in SLE Patients: A Possible Marker of Disease Activity and Organ Damage

Abstract Background Systemic lupus erythematous (SLE) is a prototypic autoimmune disease with a complex pathogenesis involving multiple genetic and environmental factors. Cell death has been regarded as an important event in lupus pathogenesis as it leads to release of antigens as nucleic acids for immune complex formation. DNA-antibody complex in the circulation are one of the hallmarks of SLE that leads to detrimental effects causing manifestations of SLE. Fluctuation in circulating DNA level might be one of the driving factors behind flare-ups of SLE. Objectives This study aims to measure the circulating cell free DNA (cf-DNA) in patients with SLE as a potential marker for disease activity and organ damage. Methods This case control study included 100 participants categorized into 75 SLE patients as patient group (Group I), further divided to 39 SLE patients without therapy (group Ia), 36 SLE patients with therapy (Group Ib) and 25 age and sex matched healthy subjects as a control group (Group II). All participants were subjected to full history taking, thorough rheumatological examination and lab assessment of complete blood count (CBC), ESR, CRP, C3, C4 levels, ANA titer, anti-ds-DNA concentration by ELIZA and measurement of plasma cf-DNA levels by real time PCR. Cf- DNA concentration is expressed as concentration (ng/ml). Results SLE patients (Group Ia and Ib) showed significant increase in (plasma cf-DNA,CRP, ESR, ANA, anti-ds-DNA), significant decrease in (C3 and C4, hemoglobin, total leucocytic count and platelet count). Plasma cf-DNA (ng/ml) was significantly lower in group Ib compared to group Ia. There was significant positive correlation between plasma cf-DNA (ng/ml) and levels of ANA and anti-ds-DNA in all SLE patients and with SLEDAI-2k score in all patients. Conclusion Plasma level of cf-DNA is significantly increased in SLE patients especially before starting therapy these data may suggest it to be a possible marker of treatment follow up. Further studies on a larger patient population are still needed to confirm these results.

Recent advances in pathogenesis, diagnosis, and therapeutic approaches for digestive system involvement in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of large amounts of autoantibodies and immune complex formation. Because of their atypical clinical symptoms, SLE patients with digestive systeminvolvement may not be recognized or treated precisely and extensively. Clinicians should pay close attention to SLE with digestive system involvement, as these conditions can easily worsen the condition and possibly endanger the patient's life. In this review we summarized the pathogenesis, pathological characteristics, clinical manifestations, diagnosis, and therapies for digestive system involvement in SLE.