What is the pathogenesis of infections and immune diseases?

From the Guidelines

The pathogenesis of infections and immune diseases in patients with systemic lupus erythematosus (SLE) involves a complex interplay between genetic susceptibility, environmental factors, and dysregulation of the innate and adaptive immune system, leading to an increased risk of infections, particularly bacterial infections, such as those caused by Streptococcus pneumoniae 1.

Key Factors Contributing to Infection Risk

• Genetic susceptibility and environmental factors contribute to the development of SLE, a chronic multi-organ autoimmune disease characterized by immune complex deposition and vasculopathy 1.
• Dysregulation of the innate and adaptive immune system, including type-1 interferon, plays a crucial role in the pathogenesis of SLE and increased infection risk 1.
• Immunosuppressant therapy, such as corticosteroids and cytotoxic drugs, commonly used in SLE management, further increases the risk of infections 1.

Mechanisms of Immune Dysregulation

• Molecular mimicry, bystander activation, epitope spreading, and persistent infection can lead to excessive inflammation or autoimmune reactions, contributing to the development of infectious immune diseases 1.
• The immune response in SLE patients can be impaired, resulting in poor and impaired responses to anti-pneumococcal vaccination, highlighting the need for careful consideration of vaccination strategies in these patients 1.

Clinical Implications

• Vaccination status should be assessed in the initial workup of patients with autoimmune conditions, including SLE, to prevent infections and reduce morbidity and mortality 1.
• The choice of pneumococcal vaccine, either pneumococcal conjugate vaccine (PCV) or pneumococcal polysaccharide vaccine (PPSV), should be guided by the patient's individual risk factors and immune status, with consideration of the potential benefits and risks of each vaccine type 1.

From the FDA Drug Label

Corticosteroids, including prednisone tablets, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens Corticosteroids can: • Reduce resistance to new infections • Exacerbate existing infections • Increase the risk of disseminated infections • Increase the risk of reactivation or exacerbation of latent infections • Mask some signs of infection Patients receiving immunosuppressants, including AZASAN, are at increased risk for bacterial, viral, fungal, protozoal, and opportunistic infections, including reactivation of latent infections.

The pathogenesis of infections and immune diseases is related to the immunosuppressive effects of corticosteroids and immunosuppressants, such as prednisone and azathioprine, which can:

• Suppress the immune system, increasing the risk of infection with various pathogens
• Reduce resistance to new infections
• Exacerbate existing infections
• Increase the risk of disseminated infections
• Reactivate latent infections
• Mask signs of infection 2, 3

From the Research

Pathogenesis of Infections

The pathogenesis of infections is a complex process that involves the interaction between the infecting organism and the host's immune system 4. This process can be understood by examining the two branches of the immune system: the innate/natural immune response and the adaptive/acquired immune response.

Immune Response

The immune response to infection involves the activation of various cell types and the production of cytokines and other molecules that help to eliminate the invading pathogen 5. The innate immune response provides immediate defense against infection, while the adaptive immune response provides long-term protection.

Intracellular Pathogens

Intracellular pathogens, such as viruses, bacteria, and parasites, can establish persistent infections by evading the host immune system and replicating inside host cells 5. These pathogens have evolved diverse immune escape strategies, including residing and multiplying inside host immune cells, primarily macrophages.

Single-Cell RNA Sequencing

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for understanding the pathogenesis of infectious diseases 6. This technology enables the analysis of cell diversity, heterogeneity of the immune response, and detailed molecular mechanisms underlying infectious diseases.

Sepsis Pathogenesis

Sepsis pathogenesis is shaped by the balance between the transcriptional states of systemic inflammation and antimicrobial response 7. Patients with sepsis differ in their clinical presentations and immune dysregulation in response to infection, but the fundamental processes that determine this heterogeneity remain elusive.

Key Factors in Pathogenesis

Some key factors that influence the pathogenesis of infections include:

• The type of infecting organism and its virulence factors
• The host's immune status and ability to mount an effective immune response
• The presence of underlying medical conditions that may predispose to infection
• The use of antibiotics and other treatments that may modulate the immune response 8
• Behavioral, social, and cultural factors that may impact the host's immune system and susceptibility to infection 8