Clinical diagnosis
Case 227
【Discussion】
The third immune defense line composes of production of IgM and IgG. The initiation of the third defense triggers cytokine production from macrophages and T cells. Macrophages and dendric cells phagocyte pathogens and the information of the antigen is transmitted to T cells and B cells. B cells differentiate to plasma cells who produce IgM, IgG and IgA. First, the production of IgM is relatively speedy and the production peak is approximately 4 to 7 days after the onset of symptoms. Its production gradually decreases and finalize in the end. Meanwhile, IgG production starts at the moment when IgM reaches peak level, gradually increases and reaches peak at 2 to 3 weeks after its production initiation. IgM owns five monomers to easily catch pathogen antigens, while IgG owns one monomer to catch the specific pathogen antigen. IgM is approximately 5-6% of all immunoglobulins and IgG, 75 to 80% in serum (1-3). IgM concentration drops soon after its production probably because more volume IgM for long cause renal disorder – glomerulosclerosis. It is considered that poor production of IgM and IgG trigger implies weakness of the third immune defense. Actually, in the procession of with COVID19, it is known that some patients worsen their symptoms suddenly approximately 5 days after the infection onset.
Chest CT demonstrate the procession of immune defense system. The early microscopic findings of the resected lung specimen obtained by surgical resection for lung cancer associated with COVID19 infection day 7 showed protein exudates (surfactant) in alveolar space, hyperplastic type II pneumocyte, mononuclear inflammatory cells (lymphocytes), multinucleated giant cells (macrophage & dendric cells) and proliferating fibroblasts with intra-alveolar fibrin (4-6). Chest CT findings of patients with COVID19 are categorized into four stages: slight homogeneous ground glass, melon skin ground glass, consolidation and consolidation with fibrotic components. Based on the microscopic findings, slight ground glass implies protein exudates (surfactant) in alveolar space. Melon skin glass opacity implies infiltration of lymphocytes, monocytes and type II pneumocytes or fibroblasts proliferating. Infiltration of inflammatory cells and formation of fibroblasts ball into alveolar space plus interstitial are found.
Consolidation with fibrotic components imply infiltration of inflammatory cells into alveolar space and fibrosis. In short, these radiologic findings of chest CT reflect the time procession of immune defense line II and III. When immune defense line IV works, chest CT will demonstrate the findings of diffuse gland glass opacity and/or consolidation in the whole lung, namely, acute respiratory distress syndrome (ARDS), implying microscopic findings of diffuse alveolar damage (DAD) (6, 7). DAD is the final stage of ARDS and COVID19. It is caused by extensive viral infection to type I pneumocytes and destructed by immune response with macrophages and chemokine
【Summary】
IgM begins to be produced by plasma cells a few days after cytokine release from macrophages and T cells. The maximum production is most 5 days after the cytokine release and decrease gradually. Ig G production begins at the time of peak of Ig M production and reaches to peak three or four weeks later. In case of insufficient production of Ig M and Ig G, the patient symptoms suddenly become worsening. Radiological findings of chest CT for patients with COVID19 are slight ground glass, ground glass irrespective of homogeneous or inhomogeneous, consolidation and consolidation with fibrous component which microscopically reveal protein exudates (surfactant) and immunoglobulins in alveolar space, proliferation of type II pneumocytes, lymphocytes, multinucleated giant cells, macrophage & dendric cells in interstitial, those both in interstitial and alveolar space, and those plus fibrosis, respectively. Diffuse alveolar damages occur when viral proliferation and cytokine storm occurs, implying acute respiratory distress syndrome.
【References】
1.Morton HC,van Egmond M and van de Winkel JG.(1997)"Structure and function of human IgA Fc receptors (Fc alpha R).". Crit.Rev.Immunol.16,423–40.
2.Komatsuda A, et al. Discrete renal deposition of IgM heavy chain and κ light chain in Waldenström macroglobulinemia (IgM-κ). Clin Kidney J. 2012 Oct; 5(5): 438–441
3.Zhang YM, et al. Clinical Significance of IgM and C3 Glomerular Deposition in Primary Focal Segmental Glomerulosclerosis. Clin J Am Soc Nephrol. 2016 Sep 7; 11(9): 1582–1589.
4.Tian S, et al. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer. Journal of Thoracic Oncology, 2020;15: 675-678.
5.Carbone M, et al. (COVID-19) Pneumonia in Two Patients With Lung Cancer. Journal of Thoracic Oncology 2020; 15: 675-67
6.Zhu N. et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020; 382: 727-733
7.Mehta H, et al. Cigarette smoking and innate immunity. Inflamm. res. 2008; 57:497–503
2021.4.7